Your browser doesn't support javascript.
loading
Ovarian Tumor Domain-Containing 7B Attenuates Pathological Cardiac Hypertrophy by Inhibiting Ubiquitination and Degradation of Krüppel-Like Factor 4.
Du, Bin-Bin; Zhang, Jie-Lei; Kong, Ling-Yao; Shi, Hui-Ting; Zhang, Dian-Hong; Wang, Xing; Yang, Chun-Lei; Li, Peng-Cheng; Yao, Rui; Liang, Cui; Wu, Lei-Ming; Huang, Zhen.
Afiliación
  • Du BB; Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
  • Zhang JL; Department of Endocrinology The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
  • Kong LY; Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
  • Shi HT; Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
  • Zhang DH; Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
  • Wang X; Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
  • Yang CL; Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
  • Li PC; Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
  • Yao R; Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
  • Liang C; Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
  • Wu LM; Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
  • Huang Z; Cardiovascular Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University Zhengzhou China.
J Am Heart Assoc ; 12(24): e029745, 2023 Dec 19.
Article en En | MEDLINE | ID: mdl-38084712
BACKGROUND: Cardiac hypertrophy (CH) is a well-established risk factor for many cardiovascular diseases and a primary cause of mortality and morbidity among older adults. Currently, no pharmacological interventions have been specifically tailored to treat CH. OTUD7B (ovarian tumor domain-containing 7B) is a member of the ovarian tumor-related protease (OTU) family that regulates many important cell signaling pathways. However, the role of OTUD7B in the development of CH is unclear. Therefore, we investigated the role of OTUD7B in CH. METHODS AND RESULTS: OTUD7B knockout mice were used to assay the role of OTUD7B in CH after transverse aortic coarctation surgery. We further assayed the specific functions of OTUD7B in isolated neonatal rat cardiomyocytes. We found that OTUD7B expression decreased in hypertrophic mice hearts and phenylephrine-stimulated neonatal rat cardiomyocytes. Furthermore, OTUD7B deficiency exacerbated transverse aortic coarctation surgery-induced myocardial hypertrophy, abnormal cardiac function, and fibrosis. In cardiac myocytes, OTUD7B knockdown promoted phenylephrine stimulation-induced myocardial hypertrophy, whereas OTUD7B overexpression had the opposite effect. An immunoprecipitation-mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Krüppel-like factor 4). Additional molecular experiments showed that OTUD7B impedes KLF4 degradation by inhibiting lysine residue at 48 site-linked ubiquitination and suppressing myocardial hypertrophy by activating the serine/threonine kinase pathway. CONCLUSIONS: These results demonstrate that the OTUD7B-KLF4 axis is a novel molecular target for CH treatment.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Coartación Aórtica / Factor 4 Similar a Kruppel Límite: Animals Idioma: En Revista: J Am Heart Assoc Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Coartación Aórtica / Factor 4 Similar a Kruppel Límite: Animals Idioma: En Revista: J Am Heart Assoc Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido