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TET1 inhibits liver fibrosis by blocking hepatic stellate cell activation.
Wang, Jingjie; Zhang, Yitong; Ma, Yanyun; Zhao, Suhan; Wang, Jiucun; Chen, Hongtan; Zhang, Jun; Liu, Jie.
Afiliación
  • Wang J; Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
  • Zhang Y; Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China.
  • Ma Y; Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China.
  • Zhao S; State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China.
  • Wang J; Department of Anthropology and Human Genetics, School of Life Sciences, Fudan University, Shanghai, China.
  • Chen H; Six-sector Industrial Research Institute, Fudan University, Shanghai, China.
  • Zhang J; Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China.
  • Liu J; State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China.
J Gastroenterol Hepatol ; 39(7): 1403-1412, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38369780
ABSTRACT
Hepatic stellate cells (HSCs) are critical regulator contributing to the onset and progression of liver fibrosis. Chronic liver injury triggers HSCs to undergo vast changes and trans-differentiation into a myofibroblast HSCs, the mechanism remains to be elucidated. This study investigated that the involvement of hydroxymethylase TET1 (ten-eleven translocation 1) in HSC activation and liver fibrosis. It is revealed that TET1 levels were downregulated in the livers in mouse models of liver fibrosis and patients with cirrhosis, as well as activated HSCs in comparison to quiescent HSCs. In vitro data showed that the inhibition of TET1 promoted the activation HSC, whereas TET1 overexpression inhibited HSC activation. Moreover, TET1 could regulate KLF2 (Kruppel-like transcription factors) transcription by promoting hydroxymethylation of its promoter, which in turn suppressed the activation of HSCs. In vivo, it is confirmed that liver fibrosis was aggravated in Tet1 knockout mice after CCl4 injection, accompanied by excessive activation of primary stellate cells, in contrast to wild-type mice. In conclusion, we suggested that TET1 plays a significant role in HSC activation and liver fibrosis, which provides a promising target for anti-fibrotic therapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas / Modelos Animales de Enfermedad / Proteínas de Unión al ADN / Células Estrelladas Hepáticas / Cirrosis Hepática Límite: Animals / Humans / Male Idioma: En Revista: J Gastroenterol Hepatol Asunto de la revista: GASTROENTEROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas / Modelos Animales de Enfermedad / Proteínas de Unión al ADN / Células Estrelladas Hepáticas / Cirrosis Hepática Límite: Animals / Humans / Male Idioma: En Revista: J Gastroenterol Hepatol Asunto de la revista: GASTROENTEROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China
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