Skip to main content
SpringerLink
Log in

CD44 and RHAMM hyaluronan receptors in human ocular surface inflammation

  • Inflammatory Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Background

CD44 and RHAMM hyaluronan (HA) receptors have been studied in several systemic diseases such as osteoarthritis and cancer. However, not too much is known about their role in ocular surface disorders. The purpose of this research was to determine if CD44 and RHAMM are implicated in human ocular surface inflammation.

Methods

Upper tarsal conjunctival epithelial samples from patients with active ocular surface inflammation (n = 17) and healthy controls (n = 14) were recovered by brush cytology. Patients were evaluated by an ophthalmologist and classified in different groups according to the etiology (immune atopic diseases or immune non-atopic diseases) and inflammation intensity (mild/moderate or severe). CD44, RHAMM, and p53 mRNAs were measured using real-time PCR.

Results

CD44, RHAMM, and p53 mRNAs were detected in all samples. In immune atopic diseases, higher levels of CD44 and RHAMM mRNAs were present, reaching a 300 % increase for RHAMM in severe inflammation (p < 0.001). In contrast, in immune non-atopic diseases, the HA receptors were downregulated. CD44 tended to decrease up to 30 % in severe patients (p = 0.06), and RHAMM decreased 40 % in severe inflammation (p = 0.021).

Conclusions

RHAMM may be implicated in severe ocular surface inflammation affecting the upper tarsal conjunctiva.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kumagai N, Fukuda K, Fujitsu Y, Yamamoto K, Nishida T (2006) Role of structural cells of the cornea and conjunctiva in the pathogenesis of vernal keratoconjunctivitis. Prog Retin Eye Res 25:165–187

    Article  CAS  PubMed  Google Scholar 

  2. Young RD, Liskova P, Pinali C, Palka BP, Palos M, Jirsova K, Hrdlickova E, Tesarova M, Elleder M, Zeman J, Meek KM, Knupp C, Quantock AJ (2011) Large proteoglycan complexes and disturbed collagen architecture in the corneal extracellular matrix of mucopolysaccharidosis type VII (Sly syndrome). Invest Ophthalmol Vis Sci 52:6720–6728

    Article  CAS  PubMed  Google Scholar 

  3. Bonetti MI (2009) Microfibrils: a cornerstone of extracellular matrix and a key to understand Marfan syndrome. Ital J Anat Embryol 114:201–224

    PubMed  Google Scholar 

  4. Jiang D, Liang J, Noble PW (2011) Hyaluronan as an immune regulator in human diseases. Physiol Rev 91:221–264

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Turley EA (1982) Purification of a hyaluronate-binding protein fraction that modifies cell social behavior. Biochem Biophys Res Commun 108:1016–1024

    Article  CAS  PubMed  Google Scholar 

  6. Pure E, Cuff CA (2007) A crucial role for CD44 in inflammation. Trends Mol Med 7:213–221

    Article  Google Scholar 

  7. Hall CL, Turley EA (1995) Hyaluronan: RHAMM mediated cell locomotion and signaling in tumorigenesis. J Neurooncol 26:221–229

    Article  CAS  PubMed  Google Scholar 

  8. Jiang J, Casalegno-Garduno R, Chen H, Schmitt A, Schmitt M, Maxwell CA (2010) Multifunctional proteins bridge mitosis with motility and cancer with inflammation and arthritis. Sci World J 10:1244–1257

    Article  CAS  Google Scholar 

  9. Godar S, Weinberg RA (2008) Filling the mosaic of p53 actions: p53 represses RHAMM expression. Cell Cycle 7:3479

    Article  PubMed  Google Scholar 

  10. Buganim Y, Rotter V (2008) RHAMM in the complex p53 cell cycle network. Cell Cycle 7:3287–3291

    Article  Google Scholar 

  11. Zhu SN, Nolle B, Duncker G (1997) Expression of adhesion molecule CD44 on human corneas. Br J Ophthalmol 81:80–84

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Lerner LE, Schwartz DM, Hwang DG, Howes EL, Stern R (1998) Hyaluronan and CD44 in the human cornea and limbal conjunctiva. Exp Eye Res 67:481–484

    Article  CAS  PubMed  Google Scholar 

  13. Ahmad S, Kolli S, Li DQ, de Paiva CS, Pryzborski S, Dimmick I, Armstrong L, Figueiredo FC, Lako M (2008) A putative role for RHAMM/HMMR as a negative marker of stem cell-containing population of human limbal epithelial cells. Stem Cells 26:1609–1619

    Article  CAS  PubMed  Google Scholar 

  14. Giannopoulos K, Li L, Bojarska-Junak A, Rolinski J, Dmoszynska A, Hus I, Greiner J, Renner C, Döhner H, Schmitt M (2006) Expression of RHAMM/CD168 and other tumor-associated antigens in patients with B-cell chronic lymphocytic leukemia. Int J Oncol 29:95–103

    CAS  PubMed  Google Scholar 

  15. Dunn S, Kolomytkin OV, Waddell DD, Marino AA (2009) Hyaluronan-binding receptors: possible involvement in osteoarthritis. Mod Rheumatol 19:151–155

    Article  CAS  PubMed  Google Scholar 

  16. Balla MM, Vemuganti GK, Kannabiran C, Honavar SG, Murthy R (2009) Phenotypic characterization of retinoblastoma for the presence of putative cancer stem-like cell markers by flow cytometry. Invest Ophthalmol Vis Sci 50:1506–1514

    Article  PubMed  Google Scholar 

  17. García-Posadas L, Contreras-Ruiz L, López-García A, Villarón Álvarez S, Maldonado M, Diebold Y (2012) Hyaluronan receptors in the human ocular surface: a descriptive and comparative study of RHAMM and CD44 in tissues, cell lines and freshly collected samples. Histochem Cell Biol 137:165–176

    Article  PubMed  Google Scholar 

  18. Efron N, Brennan NA, Hore J, Rieper K (1988) Temperature of the hyperemic bulbar conjunctiva. Curr Eye Res 7:615–618

    Article  CAS  PubMed  Google Scholar 

  19. Martinez-Osorio H, Calonge M, Corell A, Reinoso R, López A, Fernández I, San José EG, Diebold Y (2009) Characterization and short-term culture of cells recovered from human conjunctival epithelium by minimally invasive means. Mol Vis 15:2185–2195

    PubMed Central  PubMed  Google Scholar 

  20. Reinoso R, Calonge M, Castellanos E, Martino M, Fernández I, Stern ME, Corell A (2011) Differential cell proliferation, apoptosis, and immune response in healthy and evaporative-type dry eye conjunctival epithelia. Invest Ophthalmol Vis Sci 52:4819–4828

    Article  CAS  PubMed  Google Scholar 

  21. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  22. Dave B, Wynne R, Su Y, Korourian S, Chang JC, Simmen RC (2010) Enhanced mammary progesterone receptor-A isoform activity in the promotion of mammary tumor progression by dietary soy in rats. Nutr Cancer 62:774–782

    Article  CAS  PubMed  Google Scholar 

  23. Durst B, Sorg RV, Röder G, Betz B, Beckmann MW, Niederacher D, Bender HG, Dall P (2001) The influence of hormones on CD44 expression in endometrial and breast carcinomas. Oncol Rep 8:987–993

    CAS  PubMed  Google Scholar 

  24. Bollyky PL, Evanko SP, Wu RP, Potter-Perigo S, Long SA, Kinsella B, Reijonen H, Guebtner K, Teng B, Chan CK, Braun KR, Gebe JA, Nepom GT, Wight TN (2010) Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse. Cell Mol Immunol 7:211–220

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Sherman L, Sleeman J, Herrlich P, Ponta H (1994) Hyaluronate receptors: key players in growth, differentiation, migration and tumor progression. Curr Opin Cell Biol 6:726–733

    Article  CAS  PubMed  Google Scholar 

  26. Turley EA, Noble PW, Bourguignon LY (2002) Signaling properties of hyaluronan receptors. J Biol Chem 277:4589–4592

    Article  CAS  PubMed  Google Scholar 

  27. Abetamann V, Kern HF, Elsasser HP (1996) Differential expression of the hyaluronan receptors CD44 and RHAMM in human pancreatic cancer cells. Clin Cancer Res 2:1607–1618

    CAS  PubMed  Google Scholar 

  28. Hascall VC, Majors AK, de la Motte CA, Evanko SP, Wang A, Drazba JA, Strong SA, Wight TN (2004) Intracellular hyaluronan: a new frontier for inflammation? Biochim Biophys Acta 1673:3–12

    Article  CAS  PubMed  Google Scholar 

  29. Crawford GH, Pelle MT, James WD (2004) Rosacea: I. Etiology, pathogenesis, and subtype classification. J Am Acad Dermatol 51:327–341

    Article  PubMed  Google Scholar 

  30. Schenke-Layland K, Xie J, Angelis E, Starcher B, Wu K, Riemann I, MacLellan WR, Hamm-Alvarez SF (2008) Increased degradation of extracellular matrix structures of lacrimal glands implicated in the pathogenesis of Sjogren’s syndrome. Matrix Biol 27:53–66

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

Authors thank Dr. José M. Herreras, MD, PhD for helping in patient recruitment, Sonia Villarón, MD, Darío Victoria, MD and Beatriz Ramirez, MD for technical assistance in obtaining brush cytology samples. We also thank Itziar Fernández (IOBA-University of Valladolid) for statistical advice. The authors also acknowledge the assistance of Britt Bromberg, PhD, ELS, of Xenofile Editing (http://www.xenofileediting.com) for the final editing and preparation of this manuscript.

Grants

This work was supported by FEDER-CICYT Grant MAT-2010-20452-C03-01 and FPI Scholarship program (Ministry of Science and Innovation, Spain) and Regional JCyL Grant VA132A11-2.

Author information

Authors and Affiliations

  1. Ocular Surface Group, IOBA (Institute for Applied Ophthalmobiology), University of Valladolid, Valladolid, Spain

    Laura García-Posadas, Laura Contreras-Ruiz, Isabel Arranz-Valsero, Antonio López-García, Margarita Calonge & Yolanda Diebold

  2. CIBER-BBN (Biomedical Research Networking Center on Bioengineering, Biomaterials, and Nanomedicine), Valladolid, Spain

    Laura García-Posadas, Laura Contreras-Ruiz, Isabel Arranz-Valsero, Antonio López-García, Margarita Calonge & Yolanda Diebold

Authors
  1. Laura García-Posadas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Contreras-Ruiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Isabel Arranz-Valsero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antonio López-García
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Margarita Calonge
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yolanda Diebold
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yolanda Diebold.

Additional information

Authors have full control of all primary data, and agree to allow Graefe's Archive for Clinical and Experimental Ophthalmology to review their data upon request.

This study was partially presented at 2012 ARVO Annual Meeting (Fort Lauderdale, FL, USA).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

García-Posadas, L., Contreras-Ruiz, L., Arranz-Valsero, I. et al. CD44 and RHAMM hyaluronan receptors in human ocular surface inflammation. Graefes Arch Clin Exp Ophthalmol 252, 1289–1295 (2014). https://doi.org/10.1007/s00417-014-2686-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-014-2686-3

Keywords

Search

Navigation