S100A2 activation promotes interstitial fibrosis in kidneys by FoxO1-mediated epithelial-mesenchymal transition

doi:10.1007/s10565-024-09929-7

科研成果详情

题名	S100A2 activation promotes interstitial fibrosis in kidneys by FoxO1-mediated epithelial-mesenchymal transition
作者	Yang, Xuejia1; Zheng, Fan 1; Yan, Penghua2; Liu, Xueting3; Chen, Xuanwen3; Du, Xinyu3; Zhang, Yin 4; Wang, Peilei4; Chen, Chaosheng3,5; Lu, Hong2; Bai, Yongheng1,5
发表日期	2024-10-09
发表期刊	Cell Biology and Toxicology 影响因子和分区
语种	英语
原始文献类型	Article
关键词	RIF FoxO1 EMT ECM
其他关键词	MECHANISMS
摘要	BackgroundRenal interstitial fibrosis (RIF) is a common feature of chronic kidney diseases (CKD), with epithelial-mesenchymal transition (EMT) being one of its important mechanisms. S100A2 is a protein associated with cell proliferation and differentiation, but its specific functions and molecular mechanisms in RIF remain to be determined.MethodsS100A2 levels were evaluated in three mouse models, including unilateral ureteral obstruction (UUO), ischemia-reperfusion injury (IRI), and aristolochic acid nephropathy (AAN), as well as in TGF-beta 1- treated HK-2 cells and in kidney tissue samples. Furthermore, the role of S100A2 and its interaction with FoxO1 was investigated using RT-qPCR, immunoblotting, immunofluorescence staining, co-immunoprecipitation (Co-IP), transcriptome sequencing, and gain- or loss-of-function approaches in vitro.ResultsElevated expression levels of S100A2 were observed in three mouse models and TGF-beta 1-treated HK2 cells, as well as in kidney tissue samples. Following siRNA silencing of S100A2, exposure to TGF-beta 1 in cultured HK-2 cells suppressed EMT process and extracellular matrix (ECM) accumulation. Conversely, Overexpression of S100A2 induced EMT and ECM deposition. Notably, we identified that S100A2-mediated EMT depends on FoxO1. Immunofluorescence staining indicated that S100A2 and FoxO1 colocalized in the nucleus and cytoplasm, and their interaction was verified in Co-IP assay. S100A2 knockdown decreased TGF-beta 1-induced phosphorylation of FoxO1 and increased its protein expression, whereas S100A2 overexpression hampered FoxO1 activation. Furthermore, pharmacological blockade of FoxO1 rescued the induction of TGF-beta 1 on EMT and ECM deposition in S100A2 siRNA-treated cells.ConclusionS100A2 activation exacerbates interstitial fibrosis in kidneys by facilitating FoxO1-mediated EMT.Graphical abstractA schematic diagram of the underlying mechanisms by which S100A2 regulates EMT and renal fibrosis. Following injury, the cytoplasmic expression of S100A2 in renal tubular epithelial cells is markedly elevated. This increase promotes the phosphorylation of FoxO1, preventing its translocation into the nucleus and enhances EMT and extracellular matrix ECM deposition, thereby exacerbating renal interstitial fibrosis.
资助项目	Natural Science Foundation of Zhejiang province, China [LY23H050001]
出版者	SPRINGER
ISSN	0742-2091
EISSN	1573-6822
卷号	40 期号:1
DOI	10.1007/s10565-024-09929-7
页数	16
WOS类目	Cell Biology ; Toxicology
WOS研究方向	Cell Biology ; Toxicology
WOS记录号	WOS:001329362900003
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	393828
SCOPUSEID	2-s2.0-85206058661
通讯作者地址	[Bai, Yongheng]Wenzhou Med Univ, Affiliated Hosp 1, Zhejiang Key Lab Intelligent Canc Biomarker Discov, Wenzhou 325035, Peoples R China. ; [Lu, Hong]Wenzhou Med Univ, Affiliated Hosp 1, Dept Lab Med, Wenzhou 325035, Peoples R China. ; [Chen, Chaosheng]Wenzhou Med Univ, Affiliated Hosp 1, Dept Nephrol, Wenzhou 325035, Peoples R China. ; [Chen, Chaosheng;Bai, Yongheng]Wenzhou Med Univ, Inst Chron Nephropathy, Wenzhou 325035, Peoples R China.
Scopus学科分类	Toxicology;Cell Biology;Health, Toxicology and Mutagenesis
SCOPUS_ID	SCOPUS_ID:85206058661
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/220806
专题	附属第一医院附属第一医院_病理科附属第一医院_检验科附属第一医院_肾内科
通讯作者	Chen, Chaosheng; Lu, Hong; Bai, Yongheng
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 1, Zhejiang Key Lab Intelligent Canc Biomarker Discov, Wenzhou 325035, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Dept Lab Med, Wenzhou 325035, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp 1, Dept Nephrol, Wenzhou 325035, Peoples R China; 4.Wenzhou Med Univ, Affiliated Hosp 1, Dept Pathol, Wenzhou 325035, Peoples R China; 5.Wenzhou Med Univ, Inst Chron Nephropathy, Wenzhou 325035, Peoples R China
第一作者单位	附属第一医院
通讯作者单位	附属第一医院; 检验科; 肾内科; 温州医科大学
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Yang, Xuejia,Zheng, Fan,Yan, Penghua,et al. S100A2 activation promotes interstitial fibrosis in kidneys by FoxO1-mediated epithelial-mesenchymal transition[J]. Cell Biology and Toxicology,2024,40(1).
APA	Yang, Xuejia., Zheng, Fan., Yan, Penghua., Liu, Xueting., Chen, Xuanwen., ... & Bai, Yongheng. (2024). S100A2 activation promotes interstitial fibrosis in kidneys by FoxO1-mediated epithelial-mesenchymal transition. Cell Biology and Toxicology, 40(1).
MLA	Yang, Xuejia,et al."S100A2 activation promotes interstitial fibrosis in kidneys by FoxO1-mediated epithelial-mesenchymal transition".Cell Biology and Toxicology 40.1(2024).