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bioRxiv · 10.1101/2025.05.27.656052

Ninjurin2 Regulates Vascular Smooth Muscle Cell Phenotypic Switching and Vascular Remodeling through Interacting with PDGF Receptor-β

Jia, M.·Zhuo, J.·Zhao, X.·Liu, T.·Zhang, H.·Xu, K.·Wang, P.·Xu, C.
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Abstract

Vascular smooth muscle cell (VSMC) phenotypic switching from a contractile to synthetic state plays a pivotal role in vascular remodeling. Although genome-wide association studies have linked NINJ2 (encode Ninjurin2) polymorphisms are associated with risk of atherosclerosis and related conditions like ischemic stroke and coronary artery disease, its functional role in regulating VSMC plasticity remains unexplored. Here, using Ninj2 knockout (Ninj2-/-) and smooth muscle-specific overexpressing (Ninj2smcTG) mice subjected to carotid artery ligation, we demonstrate that Ninjurin2 deficiency exacerbates injury-induced intimal hyperplasia, whereas its overexpression attenuates this pathological remodeling. Mechanistically, Ninjurin2 knockdown promoted PDGF-BB-mediated VSMC phenotypic switching, proliferation, and migration, while biochemical studies revealed that Ninjurin2 interacts with PDGFR{beta} to suppress FAK signaling. These findings identify Ninjurin2 as a novel regulator of VSMC phenotypic switching via the PDGFR{beta}/FAK axis, offering new mechanistic insights into vascular remodeling and potential therapeutic avenues for atherosclerosis.

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Jia, M., Zhuo, J., Zhao, X., Liu, T., Zhang, H., Xu, K., Wang, P., Xu, C.. 2025-05-30. Ninjurin2 Regulates Vascular Smooth Muscle Cell Phenotypic Switching and Vascular Remodeling through Interacting with PDGF Receptor-β. https://doi.org/10.1101/2025.05.27.656052

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