Interaction of calcium binding protein S100A16 with myosin-9 promotes cytoskeleton reorganization in renal tubulointerstitial fibrosis
Interaction of calcium binding protein S100A16 with myosin-9 promotes cytoskeleton reorganization in renal tubulointerstitial fibrosis
复制标题
钙结合蛋白S100A16与肌球蛋白9的相互作用促进肾小管间质纤维化中的细胞骨架重组
DOI：
10.1038/s41419-020-2337-z
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发表时间：
2020-02-24
影响因子：
9
通讯作者：
Liang, Xiubin
中科院分区：
文献类型：
--
作者：
Sun, Hui;Zhao, Anran;Liang, Xiubin
Renal fibrosis arises by the generation of matrix-producing fibroblasts and myofibroblasts through the epithelial-mesenchymal transition (EMT), a process in which epithelial cells undergo a transition into a fibroblast phenotype. A key feature of the EMT is the reorganization of the cytoskeletons, which may involve the Ca2+-binding protein S100A16, a newly reported member of the S100 protein family. However, very few studies have examined the role of S100A16 in renal tubulointerstitial fibrosis. In this study, S100A16 expression was examined by immunohistochemical staining of kidney biopsy specimens from patients with various nephropathies and kidney tissues from a unilateral ureteral obstruction (UUO) mouse model. Renal histological changes were investigated in S100A16(Tg), S100A16(+/-), and WT mouse kidneys after UUO. The expression of epithelia marker E-cadherin, mesenchymal markers N-cadherin, and vimentin, extracellular matrix protein, and S100A16, as well as the organization of F-actin, were investigated in S100A16 overexpression or knockdown HK-2 cells. Mass spectrometry was employed to screen for S100A16 binding proteins in HK-2 cells. The results indicated that S100A16 is high expressed and associated with renal tubulointerstitial fibrosis in patient kidney biopsies and in those from UUO mice. S100A16 promotes renal interstitial fibrosis in UUO mice. S100A16 expression responded to increasing Ca2+ and interacted with myosin-9 during kidney injury or TGF-beta stimulation to promote cytoskeleton reorganization and EMT progression in renal tubulointerstitial fibrosis. Therefore, S100A16 is a critical regulator of renal tubulointerstitial fibroblast activation and is therefore a potential therapeutic target for the treatment of renal fibrosis.
