Role of connective tissue growth factor in the transdifferentiation of renal epithelial cells induced by transforming growth factor-β

AIM: To investigate the role of connective tissue growth factor (cTGF) in transforming growth factor-β-induced tubular-epithelial myofibroblasts trnansdifferentiation. METHODS: NRK52E cells were used and divided into several groups. The morphological changes were observed by light and electron microscopy (scanning and transmission). The expressions of cytokeratin-18 and α-SMA were measured by immunohistochemistry. RT-PCR and Western-blot were used to detect the expression of collagen type I. RESULTS: Cultured with TGF-β_1 at concentration of 10 μg/L for 3 days, part of the NRK52E cells developed elongated shape, loss of microvilli and apical-basal polarity, and appeared bundles of actin microfilaments. The addition of 10 mg/L TGF-β_1 neutralizing-antibody and 30 mg/L CTGF antisense oligonucleotides (ASON) almost completely blocked the morphological changes induced by TGF-β_1, only a little hypertrophy was observed. Cultured with 10 μg/L TGF-β_1 for 3 days, the expression of cytokeratin-18 significantly decreased, and α-SMA and collagen type I significantly increased. Treated with neutralizing-antibody, the expressions of cytokeratin-18, α-SMA and collagen type I were almost restored. Changes induced by TGF-β_1 were not reversed by CTGF sense oligonucleotides (SON). CONCLUSION: It is demonstrated that CTGF as a TGF-β downstream cytokine mediates tubular-epithelial myofibroblast transdifferentiation. [