title: Increased expression of tenascin-C-binding epithelial integrins in human bullous keratopathy corneas.
abstract: We previously found an abnormal deposition of an extracellular matrix glycoprotein, tenascin-C (TN-C), in human corneas with pseudophakic/aphakic bullous keratopathy (PBK/ABK). In this work, we studied cellular TN-C receptors in normal and PBK/ABK corneas. Cryostat sections of normal and PBK/ABK corneas were stained by immuno-fluorescence for TN-C receptors: alpha2, alpha8, alpha9, alphaVbeta3, beta1, and beta6 integrins, and annexin II. Beta6 integrin mRNA levels were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) using beta2-microglobulin gene to normalize the samples. In PBK/ABK compared to normal corneas, relatively minor changes were observed for alpha2 and beta1 integrins, and for annexin II. Alpha8, alpha9, and beta6 subunits of TN-C receptors, alpha8beta1 alpha9beta1, and alphaVbeta6, respectively, were absent from normal central corneas but were found in the central epithelium of PBK/ABK corneas. Beta6 integrin showed the most significant accumulation. It correlated best with the expression of TN-C rather than with the expression of other alphaVbeta6 ligands, fibronectin, and vitronectin. RT-PCR analysis also showed elevated levels of beta6 mRNA in PBK/ABK compared to normal corneas. Therefore, accumulation of TN-C in PBK/ABK corneas was accompanied by an increased expression of its three binding integrins, especially alphaVbeta6 in the corneal epithelium. The interaction of tenascin-C with these integrins may contribute to the fibrotic process that occurs in PBK/ABK corneas.
authors.affiliation: Ophthalmology Research Laboratories, Burns & Allen Research Institute, Cedars-Sinai Medical Center, University of California Los Angeles School of Medicine, Los Angeles, California 90048, USA. ljubimov@cshs.org
authors.forename: A V
authors.initials: AV
authors.lastname: Ljubimov
authors.forename: M
authors.initials: M
authors.lastname: Saghizadeh
authors.forename: R
authors.initials: R
authors.lastname: Pytela
authors.forename: D
authors.initials: D
authors.lastname: Sheppard
authors.forename: M C
authors.initials: MC
authors.lastname: Kenney
mesh_terms: D003316:Corneal Diseases / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D039641:Integrin beta Chains; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011946:Receptors, Antigen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin / Q000378:metabolism*
chemical_list: D039641:Integrin beta Chains; D016023:Integrins; D012333:RNA, Messenger; D011946:Receptors, Antigen; D019063:Tenascin; C028641:Tn receptor; C113256:integrin alpha 9 beta 1; C072170:integrin beta6