Sedum sarmentosum Bunge extract inhibits epithelial-mesenchymal transition and collagen accumulation in aristolochic acid-treated rat renal tubular epithelial cells
LU Hong1, HU Li-ping1, HONG Dan2, HONG Wei-long3, LIN Cheng-cheng3, WANG Si-lu3, CHEN Bi-cheng3, BAI Yong-heng3
1Department of Laboratory Medicine, 3Wenzhou Key Laboratory of Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; 2School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
AIM:To investigate the effect of Sedum sarmentosum Bunge (SSB) extract on epithelial-mesenchymal transition (EMT) and collagen accumulation induced by aristolochic acid (AA) in renal tubular epithelial cells. METHODS:Rat renal tubular epithelial NRK-52E cells were randomly divided into 3 groups, including control group (only treated with solvent), AA group (treated with AA at concentrations ranging from 1 to 100 mg/L) and SSB group (treated with AA at a concentration of 10 mg/L plus SSB extract at concentrations ranging from 10 to 2 000 mg/L). After cultured for 24 h, the morphology of the NRK-52E cells was observed under inverted phase-contrast microscope. The level of transforming growth factor β1 (TGF-β1) in the culture supernatant was measured by ELISA. Immunofluorescent analysis was performed to detect the expression of epithelial marker α-smooth muscle actin (α-SMA), mesenchymal marker E-cadherin, and extracellular cell matrix component type III collagen. The mRNA expression of E-cadherin, α-SMA, bone morphogenetic protein 7 (BMP-7) and type I collagen was also quantified by real-time PCR. RESULTS: Fibrosis-like reaction observed under microscope was obviously increased in AA-treated NRK-52E cells, and aggravated as the increase in the concentration of AA. AA at concentrations of 1 and 10 mg/L increased the expression of α-SMA, type I and type III collagens, and decreased the expression of E-cadherin. With SSB extract treatment, fibrosis in NRK-52E cells was alleviated, accompanied with the decreasing expression of α-SMA, type I and type III collagen, and the enhancing expression of E-cadherin and BMP-7.Moreover, SSB extract down-regulated TGF-β1 level in a concentration-dependent manner. CONCLUSION: AA-induced fibrosis-like reaction in renal tubular epithelial cells is reduced by the treatment with SSB extract. The possible mechanism is that SSB extract decreases TGF-β1 level, and inhibits renal EMT and collagen accumulation induced by AA.[KEY WORDS]Sedum sarmentosum Bunge|Aristolochic acid|Transforming growth factor β1|Epithelial-mesenchymal transition|Collagen
陆红,胡丽萍,洪丹,洪炜龙,林成成,王斯璐,陈必成,白永恒. 马兜铃酸诱导大鼠肾小管上皮细胞表型转化和胶原累积及垂盆草提取物的作用[J]. 中国病理生理杂志, 2013, 29(12): 2172-2178.
LU Hong, HU Li-ping, HONG Dan, HONG Wei-long, LIN Cheng-cheng, WANG Si-lu, CHEN Bi-cheng, BAI Yong-heng. Sedum sarmentosum Bunge extract inhibits epithelial-mesenchymal transition and collagen accumulation in aristolochic acid-treated rat renal tubular epithelial cells. Chin J Pathophysiol, 2013, 29(12): 2172-2178.