解剖学杂志2013,Vol.36Issue(4):711-715,5.DOI:10.3969/j.issn.1001-1633.2013.04.002
N-乙酰基-丝氨酰-天门冬氨酰-赖氨酰-脯氨酸对人肺泡Ⅱ型上皮细胞向肌成纤维细胞转化的调节作用
N-acetyl-seryl-aspartly-lysyl-proline regulates the transition from human type Ⅱ alveolar epithelial cells to myofibroblasts
摘要
Abstract
Objective:To investigate whether Ac-SDKP can regulate the ROCK/SRF/-SMA pathway mediated by TGF-β1 on EMT and play the role of anti-(Si) pulmonary fibrosis.Methods:Human type Ⅱ alveolar epithelial cells (A549) were used in the experiment.The evidence of EMT was assessed by morphology under a phase-contrast microscope.The expressions of the phenotype markers of the epithelial cells cytokeratin and mesenchymal marker vimentin,α-SMA were identified by immunocytochemistry.The expressions of E-cad,vimentin,ROCK,SRF α-SMA protein and type Ⅰ,type Ⅲ collagen were measured by Western blotting.ROCK,SRF a-SMA were also evaluated by measuring mRNA level using real-time PCR.Results:The process of EMT induced by TGF-β1 was accompanied by morphological alteration and the expression of the fibroblast phenotypic marker vimentin and myofibroblast phenotypic marker α-SMA,concomitant with a down-regulation of the epithelial phenotypic markers E-cad and cytokeratin.Compared with the control group,the expressions of ROCK,SRF,α-SMA on the level of both protein expression and gene detection increased significantly after the stimulation of TGF-β1.Collagen Ⅰ and Collagen Ⅲ were up-regulated too.While they were decreased significantly in Y-27632 (ROCK blockers) treating group and Ac-SDKP group.Conclusion:Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Rho/ROCK pathway activation.Ac-SDKP,similar to Y-27632,can inhibit the process of differentiation from epithelial cells to myofibroblasts by blocking TGF-β1 which induces ROCK/SRF/α-SMA signal transduction pathway,decreases the expressions of type Ⅰ and type Ⅲ collagen and enhances its anti-silicotic effects.关键词
N-乙酰基-丝氨酰-天门冬氨酰-赖氨酰-脯氨酸/人肺泡Ⅱ型上皮细胞/上皮-间质转化/转化生长因子-β1Key words
N-acetyl-seryl-aspartly-lysyl-proline/ human type Ⅱ alveolar epithelial cells/ epithelial-mesenchymal transition/transforming growth factor-β1引用本文复制引用
于婉莹,徐洪,邓海静,马文东,杨奕,王峥,孙月,王瑞敏,李治国..N-乙酰基-丝氨酰-天门冬氨酰-赖氨酰-脯氨酸对人肺泡Ⅱ型上皮细胞向肌成纤维细胞转化的调节作用[J].解剖学杂志,2013,36(4):711-715,5.基金项目
国家自然科学基金(81072254) (81072254)
河北省自然科学基金(C2011401024) (C2011401024)