Open AccessIMP3 promotes re‐endothelialization after arterial injury via increasing stability of VEGF mRNAhv
Author(s) -
Zhou Xinmiao,
Ye Qingqing,
Zheng Jinlei,
Kuang Lin,
Zhu Jianhua,
Yan Hui
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17225
Subject(s) - pi3k/akt/mtor pathway , apoptosis , microbiology and biotechnology , protein kinase b , medicine , cancer research , downregulation and upregulation , endothelial stem cell , messenger rna , cell migration , chemistry , signal transduction , cell , biology , in vitro , gene , biochemistry
IMP3, an RNA‐binding protein (RBP) that participates in the process of post‐transcriptional modifications of mRNA transcripts, is capable of altering cellular functions, and in some cases, be involved in specific disease progression. We aimed to investigate whether IMP3 has the ability to regulate the functional properties of endothelial cells and re‐endothelialization in response to arterial injury. Wire injury was introduced to the right carotid arteries of wildtype C57/BL6 mice. As a result, IMPs’ expressions were up‐regulated in the induced arterial lesions, and IMP3 was the most up‐regulated RNA among other IMPs. We overexpressed IMP3 before the wire‐injured surgery using adeno‐associated virus AAV2‐IMP3. In vivo studies confirmed that IMP3 overexpression accelerated the progress of re‐endothelialization after arterial injury. In vitro, endothelial cells were transfected with either ad‐IMP3 or Si‐IMP3, cell functional studies showed that IMP3 could promote endothelial cell proliferation and migration, while reducing apoptosis. Mechanistic studies also revealed that IMP3 could enhance VEGF mRNA stability and therefore up‐regulate activities of VEGF/PI3K/Akt signalling pathway. Our data indicated that IMP3 promotes re‐endothelialization after arterial injury and regulates endothelial cell proliferation, migration and apoptosis via increasing stability of VEGF mRNA and activation of VEGF/PI3K/Akt signalling pathway.