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Osteopontin: A Novel Therapeutic Target for Respiratory Diseases

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Abstract

Osteopontin (OPN) is a multifunctional phosphorylated protein that is involved in physiological and pathological events. Emerging evidence suggests that OPN also plays a critical role in the pathogenesis of respiratory diseases. OPN can be produced and secreted by various cell types in lungs and overexpression of OPN has been found in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), pulmonary hypertension (PH), pulmonary fibrosis diseases, lung cancer, lung infection, chronic obstructive pulmonary disease (COPD), and asthma. OPN exerts diverse effects on the inflammatory response, immune cell activation, fibrosis and tissue remodeling, and tumorigenesis of these respiratory diseases, and genetic and pharmacological moudulation of OPN exerts therapeutic effects in the treatment of respiratory diseases. In this review, we summarize the recent evidence of multifaceted roles and underlying mechanisms of OPN in these respiratory diseases, and targeting OPN appears to be a potential therapeutic intervention for these diseases.

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References

  1. Sécher T, Guilleminault L, Reckamp K et al (2018) Therapeutic antibodies: a new era in the treatment of respiratory diseases? Pharmacol Ther 189:149–172

    Article  PubMed  Google Scholar 

  2. Ashkar S, Weber GF, Panoutsakopoulou V et al (2000) Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 287(5454):860–864

    Article  CAS  PubMed  ADS  Google Scholar 

  3. Chen G, Zhang X, Li R et al (2010) Role of osteopontin in synovial Th17 differentiation in rheumatoid arthritis. Arthritis Rheum 62(10):2900–2908

    Article  CAS  PubMed  Google Scholar 

  4. Sawaki D, Czibik G, Pini M et al (2018) Visceral adipose tissue drives cardiac aging through modulation of fibroblast senescence by osteopontin production. Circulation 138(8):809–822

    Article  CAS  PubMed  Google Scholar 

  5. Szalay G, Sauter M, Haberland M et al (2009) Osteopontin: a fibrosis-related marker molecule in cardiac remodeling of enterovirus myocarditis in the susceptible host. Cir Res 104(7):851–859

    Article  CAS  Google Scholar 

  6. Khamissi FZ, Ning L, Kefaloyianni E et al (2022) Identification of kidney injury released circulating osteopontin as causal agent of respiratory failure. Sci Adv 8(8):eabm5900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Morse C, Tabib T, Sembrat J et al (2019) Proliferating SPP1/MERTK-expressing macrophages in idiopathic pulmonary fibrosis. Eur Respir J 54(2):1802441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fu Y, Zhang Y, Lei Z et al (2020) Abnormally activated OPN/integrin αVβ3/FAK signalling is responsible for EGFR-TKI resistance in EGFR mutant non-small-cell lung cancer. J Hematol Oncol 13(1):169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Morimoto Y, Hirahara K, Kiuchi M et al (2018) Amphiregulin-producing pathogenic memory T helper 2 cells instruct Eosinophils to secrete osteopontin and facilitate airway fibrosis. Immunity 49(1):134-150.e136

    Article  CAS  PubMed  Google Scholar 

  10. Saker M, Lipskaia L, Marcos E et al (2016) Osteopontin, a key mediator expressed by senescent pulmonary vascular cells in pulmonary hypertension. Arterioscler Thromb Vasc Biol 36(9):1879–1890

    Article  CAS  PubMed  Google Scholar 

  11. Singh A, Gill G, Kaur H et al (2018) Role of osteopontin in bone remodeling and orthodontic tooth movement: a review. Prog Orthod 19(1):18

    Article  PubMed  PubMed Central  Google Scholar 

  12. Liaw L, Birk DE, Ballas CB et al (1998) Altered wound healing in mice lacking a functional osteopontin gene (spp1). J Clin Invest 101(7):1468–1478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Shi L, Sun Z, Su W et al (2021) Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke. Immunity 54(7):1527-1542.e1528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fong YC, Liu SC, Huang CY et al (2009) Osteopontin increases lung cancer cells migration via activation of the alphavbeta3 integrin/FAK/Akt and NF-kappaB-dependent pathway. Lung Cancer 64(3):263–270

    Article  PubMed  Google Scholar 

  15. Dai J, Peng L, Fan K et al (2009) Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells. Oncogene 28(38):3412–3422

    Article  CAS  PubMed  Google Scholar 

  16. Leavenworth JW, Verbinnen B, Wang Q et al (2015) Intracellular osteopontin regulates homeostasis and function of natural killer cells. Proc Natl Acad Sci USA 112(2):494–499

    Article  CAS  PubMed  ADS  Google Scholar 

  17. Shinohara ML, Kim JH, Garcia VA et al (2008) Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin. Immunity 29(1):68–78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhao K, Zhang M, Zhang L et al (2016) Intracellular osteopontin stabilizes TRAF3 to positively regulate innate antiviral response. Sci Rep 6:23771

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  19. Rizzello C, Cancila V, Sangaletti S et al (2022) Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling. Mol Cancer 21(1):215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Christensen B, Petersen TE, Sørensen ES (2008) Post-translational modification and proteolytic processing of urinary osteopontin. Biochem J 411(1):53–61

    Article  CAS  PubMed  Google Scholar 

  21. Kaartinen MT, Pirhonen A, Linnala-Kankkunen A et al (1999) Cross-linking of osteopontin by tissue transglutaminase increases its collagen binding properties. J Biol Chem 274(3):1729–1735

    Article  CAS  PubMed  Google Scholar 

  22. Yokosaki Y, Tanaka K, Higashikawa F et al (2005) Distinct structural requirements for binding of the integrins alphavbeta6, alphavbeta3, alphavbeta5, alpha5beta1 and alpha9beta1 to osteopontin. Matrix Biol 24(6):418–427

    Article  CAS  PubMed  Google Scholar 

  23. Bayless KJ, Davis GE (2001) Identification of dual alpha 4beta1 integrin binding sites within a 38 amino acid domain in the N-terminal thrombin fragment of human osteopontin. J Biol Chem 276(16):13483–13489

    Article  CAS  PubMed  Google Scholar 

  24. Weber GF, Ashkar S, Glimcher MJ et al (1996) Receptor-ligand interaction between CD44 and osteopontin (Eta-1). Science 271(5248):509–512

    Article  CAS  PubMed  ADS  Google Scholar 

  25. Sun BS, Li Y, Zhang ZF et al (2013) Osteopontin combined with CD44v6, a novel prognostic biomarker in non-small cell lung cancer undergoing curative resection. Ann Thorac Surg 96(6):1943–1951

    Article  PubMed  Google Scholar 

  26. Kim JS, Bashir MM, Werth VP (2012) Gottron’s papules exhibit dermal accumulation of CD44 variant 7 (CD44v7) and its binding partner osteopontin: a unique molecular signature. J Invest Dermatol 132(7):1825–1832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Raineri D, Dianzani C, Cappellano G et al (2020) Osteopontin binds ICOSL promoting tumor metastasis. Commun Biol 3(1):615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mukherjee BB, Nemir M, Beninati S et al (1995) Interaction of osteopontin with fibronectin and other extracellular matrix molecules. Ann N Y Acad Sci 760:201–212

    Article  CAS  PubMed  ADS  Google Scholar 

  29. Christensen B, Nielsen MS, Haselmann KF et al (2005) Post-translationally modified residues of native human osteopontin are located in clusters: identification of 36 phosphorylation and five O-glycosylation sites and their biological implications. Biochem J 390(Pt 1):285–292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Schytte GN, Christensen B, Bregenov I et al (2020) FAM20C phosphorylation of the RGDSVVYGLR motif in osteopontin inhibits interaction with the αvβ3 integrin. J Cell Biochem. https://doi.org/10.1002/jcb.29708

    Article  PubMed  Google Scholar 

  31. Jono S, Peinado C, Giachelli CM (2000) Phosphorylation of osteopontin is required for inhibition of vascular smooth muscle cell calcification. J Biol Chem 275(26):20197–20203

    Article  CAS  PubMed  Google Scholar 

  32. Minai-Tehrani A, Chang SH, Park SB et al (2013) The O-glycosylation mutant osteopontin alters lung cancer cell growth and migration in vitro and in vivo. Int J Mol Med 32(5):1137–1149

    Article  CAS  PubMed  Google Scholar 

  33. Christensen B, Zachariae ED, Scavenius C et al (2016) Transglutaminase 2-catalyzed intramolecular cross-linking of osteopontin. Biochemistry 55(2):294–303

    Article  CAS  PubMed  Google Scholar 

  34. Higashikawa F, Eboshida A, Yokosaki Y (2007) Enhanced biological activity of polymeric osteopontin. FEBS Lett 581(14):2697–2701

    Article  CAS  PubMed  Google Scholar 

  35. Forsprecher J, Wang Z, Goldberg HA et al (2011) Transglutaminase-mediated oligomerization promotes osteoblast adhesive properties of osteopontin and bone sialoprotein. Cell Adh Migr 5(1):65–72

    Article  PubMed  PubMed Central  Google Scholar 

  36. Bos LDJ, Ware LB (2022) Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes. Lancet 400(20358):1145–1156

    Article  PubMed  Google Scholar 

  37. Wang J, Li X, Wang Y et al (2022) Osteopontin aggravates acute lung injury in influenza virus infection by promoting macrophages necroptosis. Cell Death Discov 8(1):97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hayek SS, Roderburg C, Blakely P et al (2021) Circulating osteopontin levels and outcomes in patients hospitalized for COVID-19. J Clin Med 10(17):3907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tonello S, D’Onghia D, Apostolo D et al (2023) Baseline plasma osteopontin protein elevation predicts adverse outcomes in hospitalized COVID-19 patients. Viruses 15(3):630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kasetty G, Papareddy P, Bhongir RKV et al (2019) Osteopontin protects against lung injury caused by extracellular histones. Mucosal Immunol 12(1):39–50

    Article  CAS  PubMed  Google Scholar 

  41. Hirano Y, Aziz M, Yang WL et al (2015) Neutralization of osteopontin attenuates neutrophil migration in sepsis-induced acute lung injury. Criti Care. https://doi.org/10.1186/s13054-015-0782-3

    Article  Google Scholar 

  42. Zhu Y, Wei Y, Chen J et al (2015) Osteopontin exacerbates pulmonary damage in influenza-induced lung injury. Jpn J Infect Dis 68(6):467–473

    Article  CAS  PubMed  Google Scholar 

  43. Zhao H, Chen Q, Huang H et al (2019) Osteopontin mediates necroptosis in lung injury after transplantation of ischaemic renal allografts in rats. Br J Anaesth 123(4):519–530

    Article  CAS  PubMed  Google Scholar 

  44. Kapur R, Kasetty G, Rebetz J et al (2019) Osteopontin mediates murine transfusion-related acute lung injury via stimulation of pulmonary neutrophil accumulation. Blood 134(1):74–84

    Article  CAS  PubMed  Google Scholar 

  45. Takahashi F, Takahashi K, Shimizu K et al (2004) Osteopontin is strongly expressed by alveolar macrophages in the lungs of acute respiratory distress syndrome. Lung 182(3):173–185

    Article  CAS  PubMed  Google Scholar 

  46. Yu ZX, Ji MS, Yan J et al (2015) The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome. Crit Care 19(1):82

    Article  PubMed  PubMed Central  Google Scholar 

  47. Chen L, Yang J, Zhang M et al (2023) SPP1 exacerbates ARDS via elevating Th17/Treg and M1/M2 ratios through suppression of ubiquitination-dependent HIF-1α degradation. Cytokine 164:156107

    Article  CAS  PubMed  Google Scholar 

  48. Humbert M, Guignabert C, Bonnet S et al (2019) Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives. Eur Respir J 53(1):1801887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Lorenzen JM, Nickel N, Krämer R et al (2011) Osteopontin in patients with idiopathic pulmonary hypertension. Chest 139(5):1010–1017

    Article  CAS  PubMed  Google Scholar 

  50. Bellan M, Piccinino C, Tonello S et al (2021) Role of osteopontin as a potential biomarker of pulmonary arterial hypertension in patients with systemic sclerosis and other connective tissue diseases (CTDs). Pharmaceuticals (Basel) 14(5):394

    Article  CAS  PubMed  Google Scholar 

  51. Kölmel S, Hobohm L, Käberich A et al (2019) Potential involvement of osteopontin in inflammatory and fibrotic processes in pulmonary embolism and chronic thromboembolic pulmonary hypertension. Thromb Haemost 119(8):1332–1346

    Article  PubMed  Google Scholar 

  52. Meng L, Liu X, Teng X et al (2019) Osteopontin plays important roles in pulmonary arterial hypertension induced by systemic-to-pulmonary shunt. FASEB J 33(6):7236–7251

    Article  CAS  PubMed  Google Scholar 

  53. Mura M, Cecchini MJ, Joseph M et al (2019) Osteopontin lung gene expression is a marker of disease severity in pulmonary arterial hypertension. Respirology 24(11):1104–1110

    Article  PubMed  Google Scholar 

  54. Anwar A, Li M, Frid MG et al (2012) Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 303(1):L1–L11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Peng LY, Yu M, Yang MX et al (2020) Icotinib attenuates monocrotaline-induced pulmonary hypertension by preventing pulmonary arterial smooth muscle cell dysfunction. Am J Hypertens 33(8):775–783

    Article  CAS  PubMed  Google Scholar 

  56. Matsui Y, Rittling SR, Okamoto H et al (2003) Osteopontin deficiency attenuates atherosclerosis in female apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 23(6):1029–1034

    Article  CAS  PubMed  Google Scholar 

  57. Zhao H, Wang Y, Qiu T et al (2020) Autophagy, an important therapeutic target for pulmonary fibrosis diseases. Clin Chim Acta 502:139–147

    Article  CAS  PubMed  Google Scholar 

  58. Wu M, Schneider DJ, Mayes MD et al (2012) Osteopontin in systemic sclerosis and its role in dermal fibrosis. J Invest Dermatol 132(6):1605–1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Wolak T, Kim H, Ren Y et al (2009) Osteopontin modulates angiotensin II-induced inflammation, oxidative stress, and fibrosis of the kidney. Kidney Int 76(1):32–43

    Article  CAS  PubMed  Google Scholar 

  60. Huang R, Hao C, Wang D et al (2021) SPP1 derived from silica-exposed macrophage exosomes triggers fibroblast transdifferentiation. Toxicol Appl Pharmacol 422:115559

    Article  CAS  PubMed  Google Scholar 

  61. Phan THG, Paliogiannis P, Nasrallah GK et al (2021) Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis. Cell Mol Life Sci 78(5):2031–2057

    Article  CAS  PubMed  Google Scholar 

  62. Kumar A, Elko E, Bruno SR et al (2022) Inhibition of PDIA3 in club cells attenuates osteopontin production and lung fibrosis. Thorax 77(7):669–678

    Article  PubMed  Google Scholar 

  63. Takahashi F, Takahashi K, Okazaki T et al (2001) Role of osteopontin in the pathogenesis of bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol 24(3):264–271

    Article  CAS  PubMed  Google Scholar 

  64. Hatipoglu OF, Uctepe E, Opoku G et al (2021) Osteopontin silencing attenuates bleomycin-induced murine pulmonary fibrosis by regulating epithelial-mesenchymal transition. Biomed Pharmacother 139:111633

    Article  CAS  PubMed  Google Scholar 

  65. Pardo A, Gibson K, Cisneros J et al (2005) Up-regulation and profibrotic role of osteopontin in human idiopathic pulmonary fibrosis. PloS Med 2(9):e251

    Article  PubMed  PubMed Central  Google Scholar 

  66. Hou J, Ji J, Chen X et al (2021) Alveolar epithelial cell-derived Sonic hedgehog promotes pulmonary fibrosis through OPN-dependent alternative macrophage activation. FEBS J 288(11):3530–3546

    Article  CAS  PubMed  Google Scholar 

  67. Tardelli M, Zeyda K, Moreno-Viedma V et al (2016) Osteopontin is a key player for local adipose tissue macrophage proliferation in obesity. Mol Metab 5(11):1131–1137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Nau GJ, Guilfoile P, Chupp GL et al (1997) A chemoattractant cytokine associated with granulomas in tuberculosis and silicosis. Proc Natl Acad Sci USA 94(12):6414–6419

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  69. Latoche JD, Ufelle AC, Fazzi F et al (2016) Secreted phosphoprotein 1 and sex-specific differences in silica-induced pulmonary fibrosis in mice. Environ Health Perspect 124(8):1199–1207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Dong J, Ma Q (2017) Osteopontin enhances multi-walled carbon nanotube-triggered lung fibrosis by promoting TGF-β1 activation and myofibroblast differentiation. Part Fiber Toxicol 14(1):18

    Article  Google Scholar 

  71. Khaliullin TO, Kisin ER, Murray AR et al (2017) Mediation of the single-walled carbon nanotubes induced pulmonary fibrogenic response by osteopontin and TGF-β1. Exp Lung Res 43(8):311–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Hirsch FR, Scagliotti GV, Mulshine JL et al (2017) Lung cancer: current therapies and new targeted treatments. Lancet 389(10066):299–311

    Article  CAS  PubMed  Google Scholar 

  73. Raja R, Kale S, Thorat D et al (2014) Hypoxia-driven osteopontin contributes to breast tumor growth through modulation of HIF1α-mediated VEGF-dependent angiogenesis. Oncogene 33(16):2053–2064

    Article  CAS  PubMed  Google Scholar 

  74. Qian J, LeSavage BL, Hubka KM et al (2021) Cancer-associated mesothelial cells promote ovarian cancer chemoresistance through paracrine osteopontin signaling. J Clin Invest 131(16):e146186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Hu Z, Lin D, Yuan J et al (2005) Overexpression of osteopontin is associated with more aggressive phenotypes in human non-small cell lung cancer. Clin Cancer Res 11(13):4646–4652

    Article  CAS  PubMed  Google Scholar 

  76. Gu T, Ohashi R, Cui R et al (2009) Osteopontin is involved in the development of acquired chemo-resistance of cisplatin in small cell lung cancer. Lung Cancer 66(2):176–183

    Article  PubMed  Google Scholar 

  77. Jiang YJ, Chao CC, Chang AC et al (2022) Cigarette smoke-promoted increases in osteopontin expression attract mesenchymal stem cell recruitment and facilitate lung cancer metastasis. J Adv Res 41:77–87

    Article  CAS  PubMed  ADS  Google Scholar 

  78. Boldrini L, Donati V, Dell’Omodarme M et al (2005) Prognostic significance of osteopontin expression in early-stage non-small-cell lung cancer. Br J Cancer 93(4):453–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Shijubo N, Uede T, Kon S et al (1999) Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma. Am J Respir Crit Care Med 160(4):1269–1273

    Article  CAS  PubMed  Google Scholar 

  80. Mack PC, Redman MW, Chansky K et al (2008) Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG Study S0003. J Clin Oncol 26(29):4771–4776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Isa S, Kawaguchi T, Teramukai S et al (2009) Serum osteopontin levels are highly prognostic for survival in advanced non-small cell lung cancer: results from JMTO LC 0004. J Thorac Oncol 4(9):1104–1110

    Article  PubMed  Google Scholar 

  82. Blasberg JD, Pass HI, Goparaju CM et al (2010) Reduction of elevated plasma osteopontin levels with resection of non-small-cell lung cancer. J Clin Oncol 28(6):936–941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Sun SJ, Wu CC, Sheu GT et al (2016) Integrin β3 and CD44 levels determine the effects of the OPN-a splicing variant on lung cancer cell growth. Oncotarget 7(34):55572–55584

    Article  PubMed  PubMed Central  Google Scholar 

  84. Goparaju CM, Pass HI, Blasberg JD et al (2010) Functional heterogeneity of osteopontin isoforms in non-small cell lung cancer. J Thorac Oncol 5(10):1516–1523

    Article  PubMed  PubMed Central  Google Scholar 

  85. Cui R, Takahashi F, Ohashi R et al (2007) Abrogation of the interaction between osteopontin and alphavbeta3 integrin reduces tumor growth of human lung cancer cells in mice. Lung Cancer 57(3):302–310

    Article  PubMed  Google Scholar 

  86. Senger DR, Ledbetter SR, Claffey KP et al (1996) Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin. Am J Pathol 149(1):293–305

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Blasberg JD, Goparaju CM, Pass HI et al (2010) Lung cancer osteopontin isoforms exhibit angiogenic functional heterogeneity. J Thorac Cardiovasc Surg 139(6):1587–1593

    Article  CAS  PubMed  Google Scholar 

  88. Shi L, Hou J, Wang L et al (2021) Regulatory roles of osteopontin in human lung cancer cell epithelial-to-mesenchymal transitions and responses. Clin Transl Med 11(7):e486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Qi J, Sun H, Zhang Y et al (2022) Single-cell and spatial analysis reveal interaction of FAP(+) fibroblasts and SPP1(+) macrophages in colorectal cancer. Nat Commun 13(1):1742

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  90. Pazolli E, Luo X, Brehm S et al (2009) Senescent stromal-derived osteopontin promotes preneoplastic cell growth. Cancer Res 69(3):1230–1239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Nallasamy P, Nimmakayala RK, Karmakar S et al (2021) Pancreatic tumor microenvironment factor promotes cancer stemness via SPP1-CD44 Axis. Gastroenterology 161(6):1998-2013.e1997

    Article  CAS  PubMed  Google Scholar 

  92. Matsubara E, Komohara Y, Esumi S et al (2022) SPP1 derived from macrophages is associated with a worse clinical course and chemo-resistance in lung adenocarcinoma. Cancers (Basel) 14(18):4374

    Article  CAS  PubMed  Google Scholar 

  93. Matsubara E, Yano H, Pan C et al (2023) The significance of SPP1 in lung cancers and its impact as a marker for protumor tumor-associated macrophages. Cancers (Basel) 15(8):2250

    Article  CAS  PubMed  Google Scholar 

  94. Vincent JL, Levi M, Hunt BJ (2022) Prevention and management of thrombosis in hospitalised patients with COVID-19 pneumonia. Lancet Respir Med 10(2):214–220

    Article  CAS  PubMed  Google Scholar 

  95. Gibellini L, De Biasi S, Paolini A et al (2020) Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID-19 pneumonia. EMBO Mol Med 12(12):e13001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. van der Windt GJW, Hoogerwerf JJ, de Vos AF et al (2010) Osteopontin promotes host defense during Klebsiella pneumoniae-induced pneumonia. Eur Respir J 36(6):1337–1345

    Article  PubMed  Google Scholar 

  97. van der Windt GJW, Hoogendijk AJ, Schouten M et al (2011) Osteopontin impairs host defense during pneumococcal pneumonia. J Infet Dis 203(12):1850–1858

    Article  Google Scholar 

  98. Ueno T, Miyazaki E, Ando M (2010) Osteopontin levels are elevated in patients with eosinophilic pneumonia. Respirology 15(7):1111–1121

    Article  PubMed  Google Scholar 

  99. Chang JH, Hung WY, Bai KJ et al (2016) Utility of plasma osteopontin levels in management of community-acquired pneumonia. Int J Med Sci 13(9):673–679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. MacDonald L, Alivernini S, Tolusso B et al (2021) COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes. JCI Insight 6(13):e147413

    Article  PubMed  PubMed Central  Google Scholar 

  101. Flynn JL, Chan J (2001) Immunology of tuberculosis. Annu Rev Immunol 19:93–129

    Article  CAS  PubMed  Google Scholar 

  102. O’Regan AW, Hayden JM, Body S et al (2001) Abnormal pulmonary granuloma formation in osteopontin-deficient mice. Am J Respir Crit Care Med 164(12):2243–2247

    Article  CAS  PubMed  Google Scholar 

  103. Hernández-Bazán S, Mata-Espinosa D, Lozano-Ordaz V et al (2022) Immune regulatory effect of osteopontin gene therapy in a murine model of multidrug resistant pulmonary tuberculosis. Hum Gene Ther 33(19–20):1037–1051

    Article  PubMed  Google Scholar 

  104. Koguchi Y, Kawakami K, Uezu K et al (2003) High plasma osteopontin level and its relationship with interleukin-12-mediated type 1 T helper cell response in tuberculosis. Am J Respir Crit Care Med 167(10):1355–1359

    Article  PubMed  Google Scholar 

  105. van der Windt GJ, Wieland CW, Wiersinga WJ et al (2009) Osteopontin is not crucial to protective immunity during murine tuberculosis. Immunology 128(1):e766-776

    PubMed  PubMed Central  Google Scholar 

  106. Inomata S, Shijubo N, Kon S et al (2005) Circulating interleukin-18 and osteopontin are useful to evaluate disease activity in patients with tuberculosis. Cytokine 30(4):203–211

    Article  CAS  PubMed  Google Scholar 

  107. Hasibuan FM, Shiratori B, Senoputra MA et al (2015) Evaluation of matricellular proteins in systemic and local immune response to Mycobacterium tuberculosis infection. Microbiol Immunol 59(10):623–632

    Article  CAS  PubMed  Google Scholar 

  108. Nau GJ, Liaw L, Chupp GL et al (1999) Attenuated host resistance against Mycobacterium bovis BCG infection in mice lacking osteopontin. Infect Immun 67(8):4223–4230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Christenson SA, Smith BM, Bafadhel M et al (2022) Chronic obstructive pulmonary disease. Lancet 399(10342):2227–2242

    Article  PubMed  Google Scholar 

  110. Schneider DJ, Lindsay JC, Zhou Y et al (2010) Adenosine and osteopontin contribute to the development of chronic obstructive pulmonary disease. FASEB J 24(1):70–80

    Article  PubMed  PubMed Central  Google Scholar 

  111. Lee SJ, Kim SH, Kim W et al (2014) Increased plasma osteopontin in frequent exacerbator and acute exacerbation of COPD. Clin Respir J 8(3):305–311

    Article  CAS  PubMed  Google Scholar 

  112. Shan M, Yuan X, Song LZ et al (2012) Cigarette smoke induction of osteopontin (SPP1) mediates T(H)17 inflammation in human and experimental emphysema. Sci Transl Med 4(117):117ra119

    Article  Google Scholar 

  113. Gela A, Bhongir RK, Mori M et al (2016) Osteopontin that is elevated in the airways during COPD impairs the antibacterial activity of common innate antibiotics. PloS one 11(1):e0146192

    Article  PubMed  PubMed Central  Google Scholar 

  114. Kuruvilla ME, Lee FE, Lee GB (2019) Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol 56(2):219–233

    Article  PubMed  PubMed Central  Google Scholar 

  115. Fahy JV (2015) Type 2 inflammation in asthma–present in most, absent in many. Nat Rev Immunol 15(1):57–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Delimpoura V, Bakakos P, Tseliou E et al (2010) Increased levels of osteopontin in sputum supernatant in severe refractory asthma. Thorax 65(9):782–786

    Article  PubMed  Google Scholar 

  117. Samitas K, Zervas E, Vittorakis S et al (2011) Osteopontin expression and relation to disease severity in human asthma. Eur Respir J 37(2):331–341

    Article  CAS  PubMed  Google Scholar 

  118. Kohan M, Bader R, Puxeddu I et al (2007) Enhanced osteopontin expression in a murine model of allergen-induced airway remodelling. Clin Exp Allergy 37(10):1444–1454

    Article  CAS  PubMed  Google Scholar 

  119. Trinh HKT, Nguyen TVT, Kim SH et al (2020) Osteopontin contributes to late-onset asthma phenotypes in adult asthma patients. Exp Mol Med 52(2):253–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Akelma AZ, Cizmeci MN, Kanburoglu MK et al (2014) Elevated level of serum osteopontin in school-age children with asthma. Allergol Immunopathol (Madr) 42(4):275–281

    Article  CAS  PubMed  Google Scholar 

  121. Hillas G, Loukides S, Kostikas K et al (2013) Increased levels of osteopontin in sputum supernatant of smoking asthmatics. Cytokine 61(1):251–255

    Article  CAS  PubMed  Google Scholar 

  122. Kanemitsu Y, Ito I, Niimi A et al (2014) Osteopontin and periostin are associated with a 20-year decline of pulmonary function in patients with asthma. Am J Respir Crit Care Med 190(4):472–474

    Article  PubMed  Google Scholar 

  123. Kohan M, Breuer R, Berkman N (2009) Osteopontin induces airway remodeling and lung fibroblast activation in a murine model of asthma. Am J Respir Cell Mol Biol 41(3):290–296

    Article  CAS  PubMed  Google Scholar 

  124. Simoes DC, Xanthou G, Petrochilou K (2009) Osteopontin deficiency protects against airway remodeling and hyperresponsiveness in chronic asthma. Am J Respir Crit Care Med 179(10):894–902

    Article  CAS  PubMed  Google Scholar 

  125. Yang HW, Park JH, Jo MS et al (2022) Eosinophil-derived osteopontin induces the expression of pro-inflammatory mediators and stimulates extracellular matrix production in nasal fibroblasts: the role of osteopontin in eosinophilic chronic rhinosinusitis. Front Immunol 13:777928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Puxeddu I, Berkman N, Ribatti D et al (2010) Osteopontin is expressed and functional in human eosinophils. Allergy 65(2):168–174

    Article  CAS  PubMed  Google Scholar 

  127. Xanthou G, Alissafi T, Semitekolou M et al (2007) Osteopontin has a crucial role in allergic airway disease through regulation of dendritic cell subsets. Nat Med 13(5):570–578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Gela A, Kasetty G, Mörgelin M et al (2016) Osteopontin binds and modulates functions of eosinophil-recruiting chemokines. Allergy 71(1):58–67

    Article  CAS  PubMed  Google Scholar 

  129. Kasetty G, Bhongir RKV, Papareddy P et al (2019) Osteopontin protects against pneumococcal infection in a murine model of allergic airway inflammation. Allergy 74(4):663–674

    Article  CAS  PubMed  Google Scholar 

  130. Kurokawa M, Konno S, Matsukura S et al (2009) Effects of corticosteroids on osteopontin expression in a murine model of allergic asthma. Int Arch Allergy Immunol 149(Supp 1):7–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Uwadiae FI, Pyle CJ, Walker SA et al (2019) Targeting the ICOS/ICOS-L pathway in a mouse model of established allergic asthma disrupts T follicular helper cell responses and ameliorates disease. Allergy 74(4):650–662

    Article  CAS  PubMed  Google Scholar 

  132. Bellan M, Murano F, Ceruti F et al (2022) Increased levels of ICOS and ICOSL are associated to pulmonary arterial hypertension in patients affected by connective tissue diseases. Diagnostics (Basel) 12(3):704

    Article  CAS  PubMed  Google Scholar 

  133. Tanaka C, Fujimoto M, Hamaguchi Y et al (2010) Inducible costimulator ligand regulates bleomycin-induced lung and skin fibrosis in a mouse model independently of the inducible costimulator/inducible costimulator ligand pathway. Arthritis Rheum 62(6):1723–1732

    Article  CAS  PubMed  Google Scholar 

  134. Fan X, He C, Jing W et al (2015) Intracellular osteopontin inhibits toll-like receptor signaling and impedes liver carcinogenesis. Cancer Res 75(1):86–97

    Article  CAS  PubMed  Google Scholar 

  135. Shinohara ML, Lu L, Bu J et al (2006) Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. Nat Immunol 7(5):498–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by grant 82002100 (to Yiyi Yang) from the National Natural Science Foundation of China (Beijing, China).

Funding

This work was supported by Grant No 82002100 (to Yiyi Yang) from the National Natural Science Foundation of China (Beijing, China).

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Author notes

  1. Qi Jia and Yeling Ouyang have contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Qi Jia, Yeling Ouyang, Yiyi Yang, Shanglong Yao, Xiangdong Chen & Zhiqiang Hu

  2. Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Qi Jia, Yeling Ouyang, Yiyi Yang, Shanglong Yao, Xiangdong Chen & Zhiqiang Hu

  3. Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan, 430022, China

    Qi Jia, Yeling Ouyang, Yiyi Yang, Shanglong Yao, Xiangdong Chen & Zhiqiang Hu

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  1. Qi Jia
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Contributions

QJ and ZH conceived, wrote, edited, and prepared the figures and tables in this manuscript. QJ, YO, and YY wrote the manuscript. XC, SY, and ZH edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zhiqiang Hu.

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Jia, Q., Ouyang, Y., Yang, Y. et al. Osteopontin: A Novel Therapeutic Target for Respiratory Diseases. Lung 202, 25–39 (2024). https://doi.org/10.1007/s00408-023-00665-z

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