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TEAD1 (TEA Domain Transcription Factor 1) Promotes Smooth Muscle Cell Proliferation Through Upregulating SLC1A5 (Solute Carrier Family 1 Member 5)-Mediated Glutamine Uptake.
Osman, Islam; He, Xiangqin; Liu, Jinhua; Dong, Kunzhe; Wen, Tong; Zhang, Fanzhi; Yu, Luyi; Hu, Guoqing; Xin, Hongbo; Zhang, Wei; Zhou, Jiliang.
Afiliação
  • Osman I; From the Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University (I.O., K.D., G.H., J.Z.).
  • He X; Institute of Translational Medicine (X.H., H.X.), Nanchang University, China.
  • Liu J; School of Life Sciences (X.H., H.X.), Nanchang University, China.
  • Dong K; Department of Respiratory Medicine (J.L., W.Z.), The First Affiliated Hospital of Nanchang University, China.
  • Wen T; From the Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University (I.O., K.D., G.H., J.Z.).
  • Zhang F; Department of Cardiology (T.W.), The First Affiliated Hospital of Nanchang University, China.
  • Yu L; Department of Cardiology, Jiangxi Provincial People's Hospital, Nanchang, China (F.Z.).
  • Hu G; From the Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University (I.O., K.D., G.H., J.Z.).
  • Xin H; From the Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University (I.O., K.D., G.H., J.Z.).
  • Zhang W; Institute of Translational Medicine (X.H., H.X.), Nanchang University, China.
  • Zhou J; School of Life Sciences (X.H., H.X.), Nanchang University, China.
Circ Res ; 124(9): 1309-1322, 2019 04 26.
Article em En | MEDLINE | ID: mdl-30801233
RATIONALE: TEAD (TEA domain transcription factor) 1-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 (mechanistic target of rapamycin complex 1) signaling in vivo. Using an inducible smooth muscle-specific Tead1 KO (knockout) 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 downregulates VSMC differentiation markers but also activates mTORC1 signaling, leading to enhanced VSMC proliferation. Using whole-transcriptome sequencing analysis, we identified Slc1a5 (solute carrier family 1 member 5)-a key glutamine transporter-as a novel TEAD1 target gene. SLC1A5 overexpression mimicked TEAD1 in promoting mTORC1 activation and VSMC proliferation. Moreover, depletion of SLC1A5 by silencing RNA or blocking SLC1A5-mediated glutamine uptake attenuated TEAD1-dependent mTORC1 activation and VSMC proliferation. CONCLUSIONS: Our study unravels a novel mechanism by which TEAD1 promotes VSMC proliferation via transcriptional induction of SLC1A5, thereby activating mTORC1 signaling and promoting neointima formation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Antígenos de Histocompatibilidade Menor / Sistema ASC de Transporte de Aminoácidos / Miócitos de Músculo Liso / Proliferação de Células / Proteínas de Ligação a DNA / Glutamina Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Antígenos de Histocompatibilidade Menor / Sistema ASC de Transporte de Aminoácidos / Miócitos de Músculo Liso / Proliferação de Células / Proteínas de Ligação a DNA / Glutamina Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article