| Summary: | 碩士 === 中華醫事科技大學 === 生物醫學研究所 === 99 === Background: Hyperglycemia is the most important risk factor in the progression of renal fibrosis in diabetic kidney. Based on previous studies, interleukin-7 (IL-7) may possess antifibrotic activities in pulmonary fibrosis model. However, the role of IL-7 in the pathogenesis of renal tubulointerstitial fibrosis remains unclear. Thus, we hereby elucidate the effects of IL-7 in cultured renal proximal tubular epithelial cells (designated as HK-2) treated under hyperglycemic media. Material and Methods: Cells were cultured in high glucose (HG, 27.5mM) for 2 days. Different concentration of IL-7 (10、 50、100 or 200ng/ml) was added in the last 24 hours of culture. ELISA was used to evaluate the secreted protein such as fibronectin and TGF-β1. Western blot was used to examine the EMT marker (including α-smooth muscle actin (α-SMA) and E-cadherin), signal transducer (including Smad Smad2/3 and Smad7) and EMT initiator (e.q Snail, Slug). Immunofluorescence staining was used to assay the in situ expression of proteins (e.q. α-SMA, E-cadherin and Snail). Results: We found that IL-7 significantly attenuated HG-inhibited cellular growth and HG-induced fibrosis. HG-induced up-regulation of fibronectin, TGF-β, TGF-β RII and p-smad2/3 was markedly inhibited by IL-7. On the contrary, HG-induced down-regulation of smad7 was significantly reversed by IL-7 instead. Moreover, IL-7 markedly inhibited HG-induced increase in α-smooth muscle actin and snail. Whereas HG-induced decrease in E-cadherin expression was reversed as well. Conclusion, IL-7 has the potential to inhibit high glucose-induced renal tubular fibrosis possibly by modulating Smads and EMT pathway.
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