Activated mesangial cells induce glomerular endothelial cells proliferation in rat anti‐Thy‐1 nephritis through VEGFA/VEGFR2 and Angpt2/Tie2 pathway. (13th May 2021)

• Record Type: Journal Article
• Authors: Zhao, Yinghua; Fu, Bo; Chen, Pu; Li, Qinggang; Ouyang, Qing; Zhang, Chuyue; Cai, Guangyan; Wu, Lingling; Chen, Xiangmei
• Is Part Of: Cell proliferation. Volume 54:Number 6(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-05-13
• Subjects: Angpt2/Tie2 pathway -- glomerular endothelial cells -- mesangial cells -- mesangial proliferative glomerulonephritis -- VEGFA/VEGFR2 pathway; Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.13055
• Languages: English
• ISSNs: 0960-7722

Abstract

Abstract: Objectives: We aimed to investigate the underlying mechanism of endothelial cells (ECs) proliferation in anti‐Thy‐1 nephritis. Materials and methods: We established anti‐Thy‐1 nephritis and co‐culture system to explore the underlying mechanism of ECs proliferation in vivo and in vitro. EdU assay kit was used for measuring cell proliferation. Immunohistochemical staining and immunofluorescence staining were used to detect protein expression. ELISA was used to measure the concentration of protein in serum and medium. RT‐qPCR and Western blot were used to qualify the mRNA and protein expression. siRNA was used to knock down specific protein expression. Results: In anti‐Thy‐1 nephritis, ECs proliferation was associated with mesangial cells (MCs)‐derived vascular endothelial growth factor A (VEGFA) and ECs‐derived angiopoietin2 (Angpt2). In vitro co‐culture system activated MCs‐expressed VEGFA to promote vascular endothelial growth factor receptor2 (VEGFR2) activation, Angpt2 expression and ECs proliferation, but inhibit TEK tyrosine kinase (Tie2) phosphorylation. MCs‐derived VEGFA stimulated Angpt2 expression in ECs, which inhibited Tie2 phosphorylation and promoted ECs proliferation. And decline of Tie2 phosphorylation induced ECs proliferation. In anti‐Thy‐1 nephritis, promoting Tie2 phosphorylation could alleviate ECs proliferation. Conclusions: Our study showed that activated MCs promoted ECs proliferation through VEGFA/VEGFR2 and Angpt2/Tie2 pathway in experimental mesangial proliferative glomerulonephritis (MPGN) and in vitro co‐culture system. And enhancing Tie2 phosphorylation could alleviate ECs proliferation, which will provide a new idea for MPGN treatment. Abstract : The underlying mechanism of glomerular ECs proliferation. Normally, Angpt2 was stored in the Weibel‐Palade bodies in ECs. When MCs were stimulated, they produced VEGFA which acted on the ECs surface receptor VEGFR2 to promote Angpt2 expression. Angpt2 acted on Tie2 through autocrine which inhibited Tie2 phosphorylation and caused ECs proliferation. ECs, endothelial cells. MCs, mesangial cells. VEGFA, vascular endothelial growth factor A. VEGFR2, vascular endothelial growth factor receptor2. Angpt2, angiopoietin2. Tie2, TEK tyrosine kinase.