Role of transforming growth factor-beta in transdifferentiation and fibrosis of lens epithelial cells.

摘要

PURPOSE: To determine the levels of mRNAs encoding markers of fibrosis in lens epithelial cells (LECs) from patients with anterior polar cataracts and to test whether transforming growth factor (TGF)-beta enhances the expression of mRNAs for mesenchymal markers in LECs. METHODS: LECs attached to the anterior capsules of patients with nuclear or anterior polar cataracts were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) for the expression of mRNAs encoding pathologic extracellular matrix proteins, a marker of myofibroblast transformation, growth factors, and growth factor receptors, and by western blot analysis for the proteins encoded by these mRNAs. Bovine lens epithelial explants and intact rabbit lenses cultured with or without TGF-beta1 were also subjected to RT-PCR and western blot analysis. RESULTS: The levels of fibronectin, type I collagen, and alpha-smooth muscle actin (SMA) mRNAs were higher in LECs from patients with anterior polar cataracts than in those from patients with nuclear cataracts. Expression of mRNAs for TGF-beta1, TGF-beta2, TGF-beta receptor type II, and connective tissue growth factor (CTGF) was significantly greater in anterior polar type than in nuclear type cataracts. In contrast, expression of mRNAs for epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), fibroblast growth factor (FGF)-2, and FGF receptor-1 was similar in LECs from the two types of cataracts. TGF-beta1 markedly increased the levels of fibronectin, type I collagen, and alpha-SMA mRNA in bovine lens epithelial explants and intact rabbit lenses. CONCLUSIONS: This is the first finding showing altered mRNA expression in LECs from anterior polar cataracts. Enhanced expression of TGF-beta and the TGF-beta receptor suggests that TGF-beta derived from LECs may function in an autocrine fashion as the prime mediator of transdifferentiation and pathogenesis in human LECs. Elevated levels of CTGF mRNA suggest that this growth factor may play a role in the increased deposition of extracellular matrix in metaplastic LECs.