title: Role of complement 3 in TNF-α-induced mesenchymal transition of renal tubular epithelial cells in vitro.
abstract: Injured renal tubular epithelial cells (RTECs) have been recently thought to directly contribute to the accumulation of myofibroblasts in renal tubulointerstitial fibrosis through a process of epithelial to mesenchymal transition (EMT). However, the factors inducing RTECs to undergo EMT and the underlying mechanisms need to be further elucidated. This study aimed to determine the EMT-inducing activity of proinflammatory cytokine TNF-α and the role for complement 3 (C3) in this activity in an in vitro model of human RTECs (HK-2 cells). Wild type HK-2 cells were treated with TNF-α, IFN-γ or C3a; C3 siRNA- or control siRNA-carrying HK-2 cells were treated with TNF-α. Changes in the cell morphology and phenotype were assessed by microscopy, RT-PCR, western blotting, and immunostaining. TNF-α effectively induced HK-2 cells to express C3 and to transform into morphologically myofibroblast-like cells that lost E-cadherin (a classical epithelial cell marker) expression but acquired alpha-smooth muscle actin (α-SMA, a classical myofibroblast differentiation marker) expression. C3 siRNA robustly attenuated all the morphologic and phenotypic changes induced by TNF-α but the control siRNA showed no effect. Our preliminary observations suggest that TNF-α may induce EMT in RTECs through inducing C3 expression.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China. wanjianxin7833@163.com
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wan
authors.forename: Xueli
authors.initials: X
authors.lastname: Zhou
authors.forename: Jiong
authors.initials: J
authors.lastname: Cui
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Zou
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Xu
authors.forename: Danyu
authors.initials: D
authors.lastname: You
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D003176:Complement C3 / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015820:Cadherins; D003176:Complement C3; D014409:Tumor Necrosis Factor-alpha