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IRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating EGR1 in male mice.
Ma, Zhen-Guo; Yuan, Yu-Pei; Fan, Di; Zhang, Xin; Teng, Teng; Song, Peng; Kong, Chun-Yan; Hu, Can; Wei, Wen-Ying; Tang, Qi-Zhu.
Afiliación
  • Ma ZG; Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, PR China.
  • Yuan YP; Cardiovascular Research Institute of Wuhan University, 430060, Wuhan, PR China.
  • Fan D; Hubei Key Laboratory of Metabolic and Chronic Diseases, 430060, Wuhan, PR China.
  • Zhang X; Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, PR China.
  • Teng T; Cardiovascular Research Institute of Wuhan University, 430060, Wuhan, PR China.
  • Song P; Hubei Key Laboratory of Metabolic and Chronic Diseases, 430060, Wuhan, PR China.
  • Kong CY; Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, PR China.
  • Hu C; Cardiovascular Research Institute of Wuhan University, 430060, Wuhan, PR China.
  • Wei WY; Hubei Key Laboratory of Metabolic and Chronic Diseases, 430060, Wuhan, PR China.
  • Tang QZ; Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, PR China.
Nat Commun ; 14(1): 4967, 2023 08 16.
Article en En | MEDLINE | ID: mdl-37587150
Cardiac fibrosis is a common feature of chronic heart failure. Iroquois homeobox (IRX) family of transcription factors plays important roles in heart development; however, the role of IRX2 in cardiac fibrosis has not been clarified. Here we report that IRX2 expression is significantly upregulated in the fibrotic hearts. Increased IRX2 expression is mainly derived from cardiac fibroblast (CF) during the angiotensin II (Ang II)-induced fibrotic response. Using two CF-specific Irx2-knockout mouse models, we show that deletion of Irx2 in CFs protect against pathological fibrotic remodelling and improve cardiac function in male mice. In contrast, Irx2 gain of function in CFs exaggerate fibrotic remodelling. Mechanistically, we find that IRX2 directly binds to the promoter of the early growth response factor 1 (EGR1) and subsequently initiates the transcription of several fibrosis-related genes. Our study provides evidence that IRX2 regulates the EGR1 pathway upon Ang II stimulation and drives cardiac fibrosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas de Homeodominio / Hormonas Peptídicas / Insuficiencia Cardíaca Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas de Homeodominio / Hormonas Peptídicas / Insuficiencia Cardíaca Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido