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Hyaluronan-positive plasma membrane protrusions exist on mesothelial cells in vivo

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Abstract

Previous observations of our research group showed that HAS2 and HAS3 overexpression in cultured cells induces the formation of long and numerous microvillus-like cell protrusions, which are present also in cultured cell types with naturally high hyaluronan secretion and the cell protrusions resemble those found in mesothelial cells. The aim of this study was to investigate whether these hyaluronan secreting, actin-dependent protrusions exist also in vivo. It was found that rat mesothelium in vivo is positive for hyaluronan and Has1–3. Also microvilli in rat mesothelium and live primary cultures of mesothelial cells were found to be hyaluronan positive, and the cells expressed all Has isoforms. Furthermore, ultrastructure of the cell protrusions in rat mesothelium was similar to that induced by overexpression of HAS2 and HAS3, and the number and orientation of actin filaments supporting the cell protrusions was identical. The results of this study show that HA-positive protrusions exist in vivo and support the idea that hyaluronan secretion from plasma membrane protrusions is a general process. This mechanism is potentially crucial for the normal function and maintenance of tissues and body fluids and may be utilized in many therapeutic applications.

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Abbreviations

BSA:

Bovine serum albumin

CD44:

Hyaluronan receptor, cluster of differentiation 44

DAB:

3,3′-Diaminobenzidine

GFP:

Green fluorescent protein

EM:

Electron microscope

EMT:

Epithelial to mesenchymal transition

HA:

Hyaluronan

HABC:

Hyaluronan binding complex of the cartilage aggrecan G1

HAS:

Hyaluronan synthase

HBSS:

Hank’s balanced salt solution

PB:

Phosphate buffer

References

  • Afify AM, Stern R, Michael CW (2005) Differentiation of mesothelioma from adenocarcinoma in serous effusions: the role of hyaluronic acid and CD44 localization. Diagn Cytopathol 32:145–150

    Article  PubMed  Google Scholar 

  • Albertine KH, Wiener-Kronish JP, Roos PJ, Staub NC (1982) Structure, blood supply, and lymphatic vessels of the sheep’s visceral pleura. Am J Anat 165:277–294

    Article  CAS  PubMed  Google Scholar 

  • Alho AM, Underhill CB (1989) The hyaluronate receptor is preferentially expressed on proliferating epithelial cells. J Cell Biol 108:1557–1565

    Article  CAS  PubMed  Google Scholar 

  • Ali G, Borrelli N, Riccardo G, Proietti A, Pelliccioni S, Niccoli C, Boldrini L, Lucchi M, Mussi A, Fontanini G (2013) Differential expression of extracellular matrix constituents and cell adhesion molecules between malignant pleural mesothelioma and mesothelial hyperplasia. J Thorac Oncol 8:1389–1395

    Article  CAS  PubMed  Google Scholar 

  • Almond A (2007) Hyaluronan. Cell Mol Life Sci 64:1591–1596

    Article  CAS  PubMed  Google Scholar 

  • Almond A, Deangelis PL, Blundell CD (2006) Hyaluronan: the local solution conformation determined by NMR and computer modeling is close to a contracted left-handed 4-fold helix. J Mol Biol 358:1256–1269

    Article  CAS  PubMed  Google Scholar 

  • Andrews PM, Porter KR (1973) The ultrastructural morphology and possible functional significance of mesothelial microvilli. Anat Rec 177:409–426

    Article  CAS  PubMed  Google Scholar 

  • Asplund T, Heldin P (1994) Hyaluronan receptors are expressed on human malignant mesothelioma cells but not on normal mesothelial cells. Cancer Res 54:4516–4523

    CAS  PubMed  Google Scholar 

  • Baker PM, Clement PB, Young RH (2014) Selected topics in peritoneal pathology. Int J Gynecol Pathol 33:393–401

    Article  PubMed  Google Scholar 

  • Bakkers J, Kramer C, Pothof J, Quaedvlieg NE, Spaink HP, Hammerschmidt M (2004) Has2 is required upstream of Rac1 to govern dorsal migration of lateral cells during zebrafish gastrulation. Development 131:525–537

    Article  CAS  PubMed  Google Scholar 

  • Bard JB, McBride WH, Ross AR (1983) Morphology of hyaluronidase-sensitive cell coats as seen in the SEM after freeze-drying. J Cell Sci 62:371–383

    CAS  PubMed  Google Scholar 

  • Bart G, Vico NO, Hassinen A, Pujol FM, Deen AJ, Ruusala A, Tammi RH, Squire A, Heldin P, Kellokumpu S, Tammi MI (2015) Fluorescence resonance energy transfer (FRET) and proximity ligation assays reveal functionally relevant homo- and heteromeric complexes among hyaluronan synthases HAS1, HAS2, and HAS3. J Biol Chem 290:11479–11490

    Article  CAS  PubMed  Google Scholar 

  • Bennett KL, Jackson DG, Simon JC, Tanczos E, Peach R, Modrell B, Stamenkovic I, Plowman G, Aruffo A (1995) CD44 isoforms containing exon V3 are responsible for the presentation of heparin-binding growth factor. J Cell Biol 128:687–698

    Article  CAS  PubMed  Google Scholar 

  • Breborowicz A, Korybalska K, Grzybowski A, Wieczorowska-Tobis K, Martis L, Oreopoulos DG (1996) Synthesis of hyaluronic acid by human peritoneal mesothelial cells: effect of cytokines and dialysate. Perit Dial Int 16:374–378

    CAS  PubMed  Google Scholar 

  • Breborowicz A, Wisniewska J, Polubinska A, Wieczorowska-Tobis K, Martis L, Oreopoulos DG (1998) Role of peritoneal mesothelial cells and fibroblasts in the synthesis of hyaluronan during peritoneal dialysis. Perit Dial Int 18:382–386

    CAS  PubMed  Google Scholar 

  • Cannistra SA, Ottensmeier C, Tidy J, DeFranzo B (1994) Vascular cell adhesion molecule-1 expressed by peritoneal mesothelium partly mediates the binding of activated human T lymphocytes. Exp Hematol 22:996–1002

    CAS  PubMed  Google Scholar 

  • Chen KS, Chen WS (2012) Experience in primary culture of human peritoneal mesothelial cell. Chin J Physiol 55:274–283

    PubMed  Google Scholar 

  • Clarris BJ, Fraser JR (1968) On the pericellular zone of some mammalian cells in vitro. Exp Cell Res 49:181–193

    Article  CAS  PubMed  Google Scholar 

  • Czernobilsky B, Moll R, Levy R, Franke WW (1985) Co-expression of cytokeratin and vimentin filaments in mesothelial, granulosa and rete ovarii cells of the human ovary. Eur J Cell Biol 37:175–190

    CAS  PubMed  Google Scholar 

  • Day AJ, de la Motte CA (2005) Hyaluronan cross-linking: a protective mechanism in inflammation? Trends Immunol 26:637–643

    Article  CAS  PubMed  Google Scholar 

  • de La Motte CA, Hascall VC, Calabro A, Yen-Lieberman B, Strong SA (1999) Mononuclear leukocytes preferentially bind via CD44 to hyaluronan on human intestinal mucosal smooth muscle cells after virus infection or treatment with poly(I.C). J Biol Chem 274:30747–30755

    Article  Google Scholar 

  • Evanko SP, Angello JC, Wight TN (1999) Formation of hyaluronan- and versican-rich pericellular matrix is required for proliferation and migration of vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 19:1004–1013

    Article  CAS  PubMed  Google Scholar 

  • Evanko SP, Tammi MI, Tammi RH, Wight TN (2007) Hyaluronan-dependent pericellular matrix. Adv Drug Deliv Rev 59:1351–1365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldberg RL, Toole BP (1984) Pericellular coat of chick embryo chondrocytes: structural role of hyaluronate. J Cell Biol 99:2114–2122

    Article  CAS  PubMed  Google Scholar 

  • Hedman K, Kurkinen M, Alitalo K, Vaheri A, Johansson S, Hook M (1979) Isolation of the pericellular matrix of human fibroblast cultures. J Cell Biol 81:83–91

    Article  CAS  PubMed  Google Scholar 

  • Heldin P, Pertoft H (1993) Synthesis and assembly of the hyaluronan-containing coats around normal human mesothelial cells. Exp Cell Res 208:422–429

    Article  CAS  PubMed  Google Scholar 

  • Hiltunen EL, Anttila M, Kultti A, Ropponen K, Penttinen J, Yliskoski M, Kuronen AT, Juhola M, Tammi R, Tammi M, Kosma VM (2002) Elevated hyaluronan concentration without hyaluronidase activation in malignant epithelial ovarian tumors. Cancer Res 62:6410–6413

    CAS  PubMed  Google Scholar 

  • Hjelle JT, Golinska BT, Waters DC, Steidley KR, McCarroll DR, Dobbie JW (1989) Isolation and propagation in vitro of peritoneal mesothelial cells. Perit Dial Int 9:341–347

    CAS  PubMed  Google Scholar 

  • Hou NY, Yang K, Chen T, Chen XZ, Zhang B, Mo XM, Hu JK (2011) CD133+ CD44+ subgroups may be human small intestinal stem cells. Mol Biol Rep 38:997–1004

    Article  CAS  PubMed  Google Scholar 

  • Ishihara T, Ferrans VJ, Jones M, Boyce SW, Kawanami O, Roberts WC (1980) Histologic and ultrastructural features of normal human parietal pericardium. Am J Cardiol 46:744–753

    Article  CAS  PubMed  Google Scholar 

  • Itano N, Sawai T, Yoshida M, Lenas P, Yamada Y, Imagawa M, Shinomura T, Hamaguchi M, Yoshida Y, Ohnuki Y, Miyauchi S, Spicer AP, McDonald JA, Kimata K (1999) Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem 274:25085–25092

    Article  CAS  PubMed  Google Scholar 

  • Jacobson A, Brinck J, Briskin MJ, Spicer AP, Heldin P (2000) Expression of human hyaluronan synthases in response to external stimuli. Biochem J 348(Pt 1):29–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joo YM, Lee MA, Lee YM, Kim MS, Kim SY, Jeon EH, Choi JK, Kim WH, Lee HC, Min BI, Kang HS, Kim CR (2004) Identification of chicken nebulin isoforms of the 31-residue motifs and non-muscle nebulin. Biochem Biophys Res Commun 325:1286–1291

    Article  CAS  PubMed  Google Scholar 

  • Kanamori-Katayama M, Kaiho A, Ishizu Y, Okamura-Oho Y, Hino O, Abe M, Kishimoto T, Sekihara H, Nakamura Y, Suzuki H, Forrest AR, Hayashizaki Y (2011) LRRN4 and UPK3B are markers of primary mesothelial cells. PLoS ONE 6:e25391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karvinen S, Pasonen-Seppänen S, Hyttinen JM, Pienimäki JP, Törrönen K, Jokela TA, Tammi MI, Tammi R (2003) Keratinocyte growth factor stimulates migration and hyaluronan synthesis in the epidermis by activation of keratinocyte hyaluronan synthases 2 and 3. J Biol Chem 278:49495–49504

    Article  CAS  PubMed  Google Scholar 

  • Knudson CB (1993) Hyaluronan receptor-directed assembly of chondrocyte pericellular matrix. J Cell Biol 120:825–834

    Article  CAS  PubMed  Google Scholar 

  • Koistinen V, Karna R, Koistinen A, Arjonen A, Tammi M, Rilla K (2015) Cell protrusions induced by hyaluronan synthase 3 (HAS3) resemble mesothelial microvilli and share cytoskeletal features of filopodia. Exp Cell Res 337:179–191

    Article  CAS  PubMed  Google Scholar 

  • Kultti A, Rilla K, Tiihonen R, Spicer AP, Tammi RH, Tammi MI (2006) Hyaluronan synthesis induces microvillus-like cell surface protrusions. J Biol Chem 281:15821–15828

    Article  CAS  PubMed  Google Scholar 

  • Lai KN, Szeto CC, Lai KB, Lam CW, Chan DT, Leung JC (1999) Increased production of hyaluronan by peritoneal cells and its significance in patients on CAPD. Am J Kidney Dis 33:318–324

    Article  CAS  PubMed  Google Scholar 

  • Laurent T (1989) The biology of hyaluronan. Introduction. Ciba Found Symp 143:1–20

    CAS  PubMed  Google Scholar 

  • Leavesley DI, Stanley JM, Faull RJ (1999) Epidermal growth factor modifies the expression and function of extracellular matrix adhesion receptors expressed by peritoneal mesothelial cells from patients on CAPD. Nephrol Dial Transplant 14:1208–1216

    Article  CAS  PubMed  Google Scholar 

  • Lee JY, Spicer AP (2000) Hyaluronan: a multifunctional, megaDalton, stealth molecule. Curr Opin Cell Biol 12:581–586

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Yu X, Zack DJ, Zhu H, Qian J (2008) TiGER: a database for tissue-specific gene expression and regulation. BMC Bioinform 9:271

    Article  Google Scholar 

  • Madison LD, Bergstrom-Porter B, Torres AR, Shelton E (1979) Regulation of surface topography of mouse peritoneal cells. Formation of microvilli and vesiculated pits on omental mesothelial cells by serum and other proteins. J Cell Biol 82:783–797

    Article  CAS  PubMed  Google Scholar 

  • Majors AK, Austin RC, de la Motte CA, Pyeritz RE, Hascall VC, Kessler SP, Sen G, Strong SA (2003) Endoplasmic reticulum stress induces hyaluronan deposition and leukocyte adhesion. J Biol Chem 278:47223–47231

    Article  CAS  PubMed  Google Scholar 

  • McBride WH, Bard JB (1979) Hyaluronidase-sensitive halos around adherent cells. Their role in blocking lymphocyte-mediated cytolysis. J Exp Med 149:507–515

    Article  CAS  PubMed  Google Scholar 

  • Merrilees MJ, Lemire JM, Fischer JW, Kinsella MG, Braun KR, Clowes AW, Wight TN (2002) Retrovirally mediated overexpression of versican v3 by arterial smooth muscle cells induces tropoelastin synthesis and elastic fiber formation in vitro and in neointima after vascular injury. Circ Res 90:481–487

    Article  CAS  PubMed  Google Scholar 

  • Michailova K, Wassilev W, Wedel T (1999) Scanning and transmission electron microscopic study of visceral and parietal peritoneal regions in the rat. Ann Anat 181:253–260

    Article  CAS  PubMed  Google Scholar 

  • Mikula-Pietrasik J, Sosinska P, Ksiazek K (2014) Resveratrol inhibits ovarian cancer cell adhesion to peritoneal mesothelium in vitro by modulating the production of α5β1 integrins and hyaluronic acid. Gynecol Oncol 134:624–630

    Article  CAS  PubMed  Google Scholar 

  • Morgelin M, Paulsson M, Heinegard D, Aebi U, Engel J (1995) Evidence of a defined spatial arrangement of hyaluronate in the central filament of cartilage proteoglycan aggregates. Biochem J 307(Pt 2):595–601

    Article  PubMed  PubMed Central  Google Scholar 

  • Mullen AJ, Barton PJ (2000) Structural characterization of the human fast skeletal muscle troponin I gene (TNNI2). Gene 242:313–320

    Article  CAS  PubMed  Google Scholar 

  • Mutsaers SE (2002) Mesothelial cells: their structure, function and role in serosal repair. Respirology 7:171–191

    Article  PubMed  Google Scholar 

  • Mutsaers SE (2004) The mesothelial cell. Int J Biochem Cell Biol 36:9–16

    Article  CAS  PubMed  Google Scholar 

  • Mutsaers SE, Wilkosz S (2007) Structure and function of mesothelial cells. Cancer Treat Res 134:1–19

    CAS  PubMed  Google Scholar 

  • Mutsaers SE, Whitaker D, Papadimitriou JM (1996) Changes in the concentration of microvilli on the free surface of healing mesothelium are associated with alterations in surface membrane charge. J Pathol 180:333–339

    Article  CAS  PubMed  Google Scholar 

  • Nga ME, Lim GS, Soh CH, Kumarasinghe MP (2008) HBME-1 and CK19 are highly discriminatory in the cytological diagnosis of papillary thyroid carcinoma. Diagn Cytopathol 36:550–556

    Article  PubMed  Google Scholar 

  • Nykopp TK, Rilla K, Tammi MI, Tammi RH, Sironen R, Hamalainen K, Kosma VM, Heinonen S, Anttila M (2010) Hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in the accumulation of hyaluronan in endometrioid endometrial carcinoma. BMC Cancer 10:512

    Article  PubMed  PubMed Central  Google Scholar 

  • Ohtsuka A, Yamana S, Murakami T (1997) Localization of membrane-associated sialomucin on the free surface of mesothelial cells of the pleura, pericardium, and peritoneum. Histochem Cell Biol 107:441–447

    Article  CAS  PubMed  Google Scholar 

  • Pappas CT, Bliss KT, Zieseniss A, Gregorio CC (2011) The Nebulin family: an actin support group. Trends Cell Biol 21:29–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pienimäki JP, Rilla K, Fulop C, Sironen RK, Karvinen S, Pasonen S, Lammi MJ, Tammi R, Hascall VC, Tammi MI (2001) Epidermal growth factor activates hyaluronan synthase 2 in epidermal keratinocytes and increases pericellular and intracellular hyaluronan. J Biol Chem 276:20428–20435

    Article  PubMed  Google Scholar 

  • Qu C, Rilla K, Tammi R, Tammi M, Kröger H, Lammi MJ (2014) Extensive CD44-dependent hyaluronan coats on human bone marrow-derived mesenchymal stem cells produced by hyaluronan synthases HAS1, HAS2 and HAS3. Int J Biochem Cell Biol 48:45–54

    Article  CAS  PubMed  Google Scholar 

  • Rilla K, Siiskonen H, Spicer AP, Hyttinen JM, Tammi MI, Tammi RH (2005) Plasma membrane residence of hyaluronan synthase is coupled to its enzymatic activity. J Biol Chem 280:31890–31897

    Article  CAS  PubMed  Google Scholar 

  • Rilla K, Tiihonen R, Kultti A, Tammi M, Tammi R (2008) Pericellular hyaluronan coat visualized in live cells with a fluorescent probe is scaffolded by plasma membrane protrusions. J Histochem Cytochem 56:901–910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rilla K, Pasonen-Seppänen S, Deen AJ, Koistinen VV, Wojciechowski S, Oikari S, Kärnä R, Bart G, Törrönen K, Tammi RH, Tammi MI (2013) Hyaluronan production enhances shedding of plasma membrane-derived microvesicles. Exp Cell Res 319:2006–2018

    Article  CAS  PubMed  Google Scholar 

  • Roth J (1973) Ultrahistochemical demonstration of saccharide components of complex carbohydrates at the alveolar cell surface and at the mesothelial cell surface of the pleura visceralis of mice by means of concanavalin A. Exp Pathol (Jena) 8:157–167

    CAS  Google Scholar 

  • Satoh K, Arai H, Nagai H, Ito M, Sato H, Motomiya M, Konno K (1987) Acid glycosaminoglycans in experimental pleural effusions. Lung 165:191–199

    Article  CAS  PubMed  Google Scholar 

  • Slater ND, Cope GH, Raftery AT (1991) Mesothelial hyperplasia in response to peritoneal dialysis fluid: a morphometric study in the rat. Nephron 58:466–471

    Article  CAS  PubMed  Google Scholar 

  • Spicer AP, Tien JY (2004) Hyaluronan and morphogenesis. Birth Defects Res C Embryo Today 72:89–108

    Article  CAS  PubMed  Google Scholar 

  • Stefancsik R, Randall JD, Mao C, Sarkar S (2003) Structure and sequence of the human fast skeletal troponin T (TNNT3) gene: insight into the evolution of the gene and the origin of the developmentally regulated isoforms. Comp Funct Genom 4:609–625

    Article  CAS  Google Scholar 

  • Stoll SW, Rittie L, Johnson JL, Elder JT (2012) Heparin-binding EGF-like growth factor promotes epithelial–mesenchymal transition in human keratinocytes. J Investig Dermatol 132:2148–2157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tammi R, Ågren UM, Tuhkanen AL, Tammi M (1994) Hyaluronan metabolism in skin. Prog Histochem Cytochem 29:1–81

    Article  CAS  PubMed  Google Scholar 

  • Teder P, Vandivier RW, Jiang D, Liang J, Cohn L, Pure E, Henson PM, Noble PW (2002) Resolution of lung inflammation by CD44. Science 296:155–158

    Article  CAS  PubMed  Google Scholar 

  • Tien JY, Spicer AP (2005) Three vertebrate hyaluronan synthases are expressed during mouse development in distinct spatial and temporal patterns. Dev Dyn 233:130–141

    Article  CAS  PubMed  Google Scholar 

  • Toole BP (2004) Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer 4:528–539

    Article  CAS  PubMed  Google Scholar 

  • Törrönen K, Nikunen K, Kärnä R, Tammi M, Tammi R, Rilla K (2014) Tissue distribution and subcellular localization of hyaluronan synthase isoenzymes. Histochem Cell Biol 141:17–31

    Article  PubMed  Google Scholar 

  • Tuuminen R, Syrjälä S, Krebs R, Arnaudova R, Rouvinen E, Nykänen AI, Lemström KB (2013) Combined donor simvastatin and methylprednisolone treatment prevents ischemia-reperfusion injury in rat cardiac allografts through vasculoprotection and immunomodulation. Transplantation 95:1084–1091

    Article  CAS  PubMed  Google Scholar 

  • Uhlen M, Oksvold P, Fagerberg L, Lundberg E, Jonasson K, Forsberg M, Zwahlen M, Kampf C, Wester K, Hober S, Wernerus H, Bjorling L, Ponten F (2010) Towards a knowledge-based human protein atlas. Nat Biotechnol 28:1248–1250

    Article  CAS  PubMed  Google Scholar 

  • Viola M, Vigetti D, Genasetti A, Rizzi M, Karousou E, Moretto P, Clerici M, Bartolini B, Pallotti F, De Luca G, Passi A (2008) Molecular control of the hyaluronan biosynthesis. Connect Tissue Res 49:111–114

    Article  CAS  PubMed  Google Scholar 

  • Wang NS (1974) The regional difference of pleural mesothelial cells in rabbits. Am Rev Respir Dis 110:623–633

    CAS  PubMed  Google Scholar 

  • Wang PM, Lai-Fook SJ (1998) Effects of ventilation on hyaluronan and protein concentration in pleural liquid of anesthetized and conscious rabbits. Lung 176:309–324

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Itano N, Narimatsu H, Kudo T, Morozumi K, Hirohashi S, Ochiai A, Ueda M, Kimata K (2004) Elevated transcript level of hyaluronan synthase1 gene correlates with poor prognosis of human colon cancer. Clin Exp Metastasis 21:57–63

    Article  CAS  PubMed  Google Scholar 

  • Yanez-Mo M, Lara-Pezzi E, Selgas R, Ramirez-Huesca M, Dominguez-Jimenez C, Jimenez-Heffernan JA, Aguilera A, Sanchez-Tomero JA, Bajo MA, Alvarez V, Castro MA, del Peso G, Cirujeda A, Gamallo C, Sanchez-Madrid F, Lopez-Cabrera M (2003) Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. N Engl J Med 348:403–413

    Article  PubMed  Google Scholar 

  • Yung S, Chan TM (2011) Pathophysiology of the peritoneal membrane during peritoneal dialysis: the role of hyaluronan. J Biomed Biotechnol 2011:180594

    Article  PubMed  PubMed Central  Google Scholar 

  • Yung S, Coles GA, Williams JD, Davies M (1994) The source and possible significance of hyaluronan in the peritoneal cavity. Kidney Int 46:527–533

    Article  CAS  PubMed  Google Scholar 

  • Yung S, Thomas GJ, Davies M (2000) Induction of hyaluronan metabolism after mechanical injury of human peritoneal mesothelial cells in vitro. Kidney Int 58:1953–1962

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge funding from the Academy of Finland (Grant #276426), Spearhead Funds from the University of Eastern Finland (Cancer Center of Eastern Finland) and Sigrid Juselius foundation. The authors want to thank Eija Rahunen and Virpi Miettinen for technical assistance and Lasse Hämäläinen and Leena Rauhala for helping with the isolation of primary cells.

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  1. Institute of Biomedicine, University of Eastern Finland, P.O.B. 1627, 70211, Kuopio, Finland

    Ville Koistinen, Tiina Jokela, Sanna Oikari, Riikka Kärnä, Markku Tammi & Kirsi Rilla

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  1. Ville Koistinen
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  2. Tiina Jokela
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Koistinen, V., Jokela, T., Oikari, S. et al. Hyaluronan-positive plasma membrane protrusions exist on mesothelial cells in vivo. Histochem Cell Biol 145, 531–544 (2016). https://doi.org/10.1007/s00418-016-1405-z

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