The role of IL-7 in renal proximal tubule epithelial cells fibrosis

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 exert 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 condition. Methods: Cells were cultured in high glucose (27.5 mM) for 2 days. Different concentration of IL-7 (10, 50, 100 or 200 ng/ml) was added in the last 24 h of culture. ELISA was used to evaluate the secreted protein such as fibronectin and TGF-beta(1). Western blot was used to examine the EMT marker (including alpha-smooth muscle actin (alpha-SMA) and E-cadherin), signal transducer (including Smad Smad2/3 and Smad7) and EMT initiator (e.g. Snail). Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin and Snail). Results: We found that IL-7 significantly attenuated high glucose-inhibited cellular growth and high glucose-induced fibrosis. More importantly, high glucose-induced up-regulation of fibronectin, TGF-beta, TGF-beta RII and pSmad2/3 was markedly inhibited by IL-7. On the contrary, high glucose-induced down-regulation of Smad7 was significantly reversed by IL-7 instead. IL-7 markedly inhibited high glucose-induced increase in alpha-SMA and Snail and decrease in E-cadherin. Conclusion: We demonstrate that IL-7 has the potential to inhibit high glucose-induced renal proximal tubular fibrosis partly by modulating Smads and EMT pathway. (c) 2011 Elsevier Ltd. All rights reserved.