Lipoxin A <sub> 4 </ Sub> Of Ctgf And Tgf-beta <sub> 1 </ Sub>-induced Human Renal Tubular Epithelial Cell Transdifferentiation Impact

【Abstract】Objective To investigate the effects of lipoxin A₄ (LXA₄) on epithelial- myofibroblast transdifferentiation (EMT) induced by recombinant human connective tissue growth factor (CTGF) in human renal proximal tubular epithelial cell line (HK2 cells) in vitro. Methods The cultured HK2 cells were stimulated with CTGF for 48 hours with or without pretreatment of LXA₄ at concentration of 100ng/ml . The morphological changes were observed under an inverted microscope. The expressions of E-cadherin,α-smooth muscle actin(α-SMA) were detected by RT-PCR and Western blot. Results CTGF induced the morphological changes of HK2 cells from oval to fusiform and stellate appearance, down-regulated the E-cadherin expression and up-regulatedα-SMA expression. The expressions of mRNA and protein of E-cadherin reduced by CTGF (0.067±0.015 and 0.257±0.221, respectively) were increased by pretreatment of the cells with LXA₄ at 100ng/ml (0.270±0.082 and 0.827±0.177 respectively, P<0.05). The expressions of mRNA and protein ofα-SMA stimulated by CTGF (0.653±0.256 and 0.167±0.050, respectively) were inhibited by LXA₄ (0.070±0.046 and 0.023±0.023, respectively, P<0.05). Conclusion LXA₄ inhibited the EMT of HK2 cells induced by CTGF. It suggests that inhibition of LXA₄ on CTGF-induced EMT could be a therapeutic strategy against tubulointerstitial fibrosis. 【Abstract】Objective To investigate the effects of lipoxin A₄ (LXA₄) on epithelial- myofibroblast transdifferentiation (EMT) induced by transforming growth factorβ₁ (TGF-β₁) in human renal tubular epithelial cell line (HK2) in vitro. Methods The cultured HK2 cells were stimulated with TGF-β₁ for 72 hours with or without pretreatment of LXA₄. The morphological changes were observed under an inverted microscope. The expressions ofα-smooth muscle actin(α-SMA) were detected by RT-PCR. Results TGF-β₁ induced the morphological changes of HK2 cells from oval to fusiform and stellate appearance, up-regulatedα-SMA expression. The expressions of mRNA ofα-SMA stimulated by TGF-β₁ (0.142±0.031) were not regulated by pretreatment of the cells with LXA₄ (0.132±0.025, 0.139±0.022, 0.136±0.015, 0.135±0.017, respectively, P>0.05) at different concentration(10, 50, 100, 500ng/ml). Conclusion LXA₄ did not inhibit the EMT of HK2 cells induced by TGF-β₁.