TEA Domain Transcription Factor 1 (TEAD1) Promotes Smooth Muscle Cell Proliferation through Up-Regulating SLC1A5-Mediated Glutamine Uptake

Rationale: TEA Domain Transcription Factor 1 (TEAD1), a major effector of the Hippo signaling pathway, acts as an oncoprotein in a variety of tumors. However, the function of TEAD1 in vascular smooth muscle cells (VSMCs) remains unclear. Objective: To assess the role of TEAD1 in vascular injury-induced smooth muscle proliferation and delineate the mechanisms underlying its action. Methods and Results: We found that TEAD1 expression is enhanced in mouse femoral artery after wire injury and correlates with the activation of mTORC1 signaling in vivo. Using an inducible smooth muscle-specific TEAD1 knock-out mouse model, we found that specific deletion of TEAD1 in adult VSMCs is sufficient to attenuate arterial injury-induced neointima formation due to inhibition of mTORC1 activation and VSMC proliferation. Furthermore, we found that TEAD1 plays a unique role in VSMCs, where it not only down-regulates VSMC differentiation markers, but it also activates mTORC1 signaling, leading to enhanced VSMC proliferation....