Involvement of TGF-β receptor- and integrin-mediated signaling pathways in the pathogenesis of granular corneal dystrophy II

Seung il Choi, Yeong Min Yoo, Bong Yoon Kim, Tae im Kim, Hyun ju Cho, So yoen Ahn, Hyung Keun Lee, Hyun Soo Cho, Eung Kweon Kim

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


PURPOSE. The purpose of this study was to elucidate the pathophysiological process in primary cultured corneal fibroblasts (PCFs) from normal subjects and granular corneal dystrophy (GCD) II patients, by using cDNA microarrays. METHODS. PCFs were isolated from the corneas of normal subjects and GCD II patients who were heterozygous and homozygous for the TGFBI R124H mutation. RNA was isolated from each sample, and gene expression profiles were analyzed with a cDNA microarray consisting of approximately 29,000 genes. Cell adhesion assays were performed to confirm the functionality of the detected gene expression profiles. RESULTS. Twofold differences were detected in the expression of 555 genes between wild-type and homozygous GCD II PCFs. Of these, 319 genes were upregulated, and 236 genes were downregulated in the homozygous GCD II PCFs. The most abundant and consistent changes were observed in gene families encoding signal transduction pathways involving the TGF- β receptor- and integrin-mediated signaling, cell differentiation and proliferation, immune responses, cell adhesion, extracellular matrix (ECM) proteolytic enzymes, cell cycle, cytoskeletal organization, mitochondrial energy metabolism, collagen catabolism, response to wounding, response to oxidative stress, and the ubiquitin-mediated proteasomal degradation pathway. Cell adhesion assays demonstrated that heterozygous and homozygous GCD II PCFs strongly attached to collagen-I, collagen-IV, fibronectin, and laminin, compared with wild-type cells. CONCLUSIONS. Alterations in the TGF- β receptor- and integrinmediated signaling pathway may play a key role in GCD II pathophysiology. If the novel factors identified in this study are involved in GCD II pathogenesis, they could assist in designing further studies to elucidate specific mechanisms of this disease.

Original languageEnglish
Pages (from-to)1832-1847
Number of pages16
JournalInvestigative Ophthalmology and Visual Science
Issue number4
Publication statusPublished - 2010 Apr

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Involvement of TGF-β receptor- and integrin-mediated signaling pathways in the pathogenesis of granular corneal dystrophy II'. Together they form a unique fingerprint.

Cite this