PTPN14 aggravates neointimal hyperplasia via boosting PDGFRβ signaling in smooth muscle cells

Qiannan Ma, Xue He, Xue Wang, Guobing Zhao, Yanhong Zhang, Chao Su, Minxin Wei, Kai Zhang, Ming Liu (), Yi Zhu () and Jinlong He ()
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Qiannan Ma: Tianjin Medical University
Xue He: Tianjin Medical University
Xue Wang: Tianjin Medical University
Guobing Zhao: Tianjin Medical University
Yanhong Zhang: Tianjin Medical University
Chao Su: The University of Hong Kong-Shenzhen Hospital
Minxin Wei: The University of Hong Kong-Shenzhen Hospital
Kai Zhang: Tianjin Medical University
Ming Liu: Tianjin Medical University General Hospital
Yi Zhu: Tianjin Medical University
Jinlong He: Tianjin Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-51881-x

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