新生内膜增生
癌症研究
蛋白质酪氨酸磷酸酶
新生内膜
细胞生物学
下调和上调
信号转导
磷酸化
血小板源性生长因子受体
增生
生物
医学
受体
内分泌学
内科学
生长因子
生物化学
基因
再狭窄
支架
作者
Qiannan Ma,Xue He,Sheng Wang,Guobing Zhao,Yanhong Zhang,Chao Su,Minxin Wei,Kai Zhang,Ming Liu,Yi Zhu,Jinlong He
标识
DOI:10.1038/s41467-024-51881-x
摘要
Smooth muscle cell (SMC) phenotypic modulation, primarily driven by PDGFRβ signaling, is implicated in occlusive cardiovascular diseases. However, the promotive and restrictive regulation mechanism of PDGFRβ and the role of protein tyrosine phosphatase non-receptor type 14 (PTPN14) in neointimal hyperplasia remain unclear. Our study observes a marked upregulation of PTPN14 in SMCs during neointimal hyperplasia. PTPN14 overexpression exacerbates neointimal hyperplasia in a phosphatase activity-dependent manner, while SMC-specific deficiency of PTPN14 mitigates this process in mice. RNA-seq indicates that PTPN14 deficiency inhibits PDGFRβ signaling-induced SMC phenotypic modulation. Moreover, PTPN14 interacts with intracellular region of PDGFRβ and mediates its dephosphorylation on Y692 site. Phosphorylation of PDGFRβY692 negatively regulates PDGFRβ signaling activation. The levels of both PTPN14 and phospho-PDGFRβY692 are correlated with the degree of stenosis in human coronary arteries. Our findings suggest that PTPN14 serves as a critical modulator of SMCs, promoting neointimal hyperplasia. PDGFRβY692, dephosphorylated by PTPN14, acts as a self-inhibitory site for controlling PDGFRβ activation. PDGF signaling plays a vital role in promoting neointimal hyperplasia. Here the authors show that PTPN14 dephosphorylates PDGFRβ Y692, which enhances PDGFRβ signaling activation, thereby aggravating neointimal hyperplasia.
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