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OTUD7B (Cezanne) ameliorates fibrosis after myocardial infarction via FAK-ERK/P38 MAPK signaling pathway.
Zhang, Jiayan; Zha, Yafang; Jiao, Yuheng; Li, Yanyan; Wang, Jian; Zhang, Song.
Afiliação
  • Zhang J; Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
  • Zha Y; Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
  • Jiao Y; Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
  • Li Y; Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China.
  • Wang J; Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
  • Zhang S; Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. Electronic address: zhangsong3961@xinhuamed.com.cn.
Arch Biochem Biophys ; 724: 109266, 2022 07 30.
Article em En | MEDLINE | ID: mdl-35523269
ABSTRACT
Fibrosis is one of the crucial reasons for cardiac dysfunction after myocardial infarction (MI). Understanding the underlying molecular mechanism that causes fibrosis is crucial to developing effective therapy. Recently, OUT domain-containing 7B (OTUD7B), also called Cezanne, a multifunctional deubiquitylate, has been found to play various roles in cancer and vascular diseases and control many important signaling pathways, including inflammation, proliferation, and so on. However, whether OTUD7B plays a role in fibrosis caused by MI remains unclear. Our study aimed to explore the function of OTUD7B in cardiac fibrosis and investigate the underlying mechanism. We found that the expression of OTUD7B was downregulated in the MI rat model and cultured cardiac fibroblasts (CFs) in hypoxic conditions and after TGF-ß1 treatment. In vitro, silencing OTUD7B using small interfering RNA (siRNA) increased α-SMA (smooth muscle actin α) and collagen Ⅰ levels in CFs, whereas the overexpression of OTUD7B using adenovirus decreased their expression. Mechanistically, OTUD7B could regulate the phosphorylation of focal adhesion kinase (FAK), a non-receptor tyrosine kinase that has been proved to act as a potential mediator of fibrosis, and ERK/P38 MAPK was involved in this regulation process. In vitro, overexpression of OTUD7B downregulated the phosphorylation level of FAK and then inhibited ERK/P38 phosphorylation, thus leading to decreased α-SMA and collagen Ⅰ expressions, while OTUD7B knockdown showed an opposite result. These findings suggest that OTUD7B could become a potentially effective therapeutic strategy against fibrosis after MI.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Endopeptidases / Infarto do Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Arch Biochem Biophys Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Endopeptidases / Infarto do Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Arch Biochem Biophys Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China