Transcription factor YY1 accelerates hepatic fibrosis development by activating NLRP3 inflammasome-mediated pyroptosis.

Fu, Xiao; Xiao, Ping; Luo, Xin; Guo, Ninghong

Fu, Xiao; Xiao, Ping; Luo, Xin; Guo, Ninghong.

Afiliación

Fu X; General Medicine Department, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, PR China.
Xiao P; General Medicine Department, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, PR China.
Luo X; General Medicine Department, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, PR China.
Guo N; Clinical Trial Center, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, PR China. guoninghong1122@163.com.

Histol Histopathol ; 39(8): 1079-1087, 2024 Aug.

Article en En | MEDLINE | ID: mdl-38264929

ABSTRACT

ABSTRACT

Hepatic fibrosis is the basis of multiple liver diseases and may eventually develop into hepatocellular carcinoma. Hepatic stellate cell (HSC) activation is a driving factor of hepatic fibrogenesis. In the liver microenvironment, liver cells and others play a crucial role in HSC activation. The liver tissues of CCl4-induced rats show excessive fibrosis, inflammation, and cell apoptosis. Yin Yang 1 (YY1) was highly expressed in hepatic fibrosis rats and TGF-ß1-treated liver cells. In animal experiments, YY1 knockdown effectively attenuated CCl4-induced liver injury and pyroptosis-related IL-1ß and IL-18 expression. In cellular experiments, NLRP3 inflammasome-mediated pyroptosis was activated by TGF-ß1 treatment, while YY1 knockdown significantly inhibited the activation of the NLRP3 inflammasome, pyroptosis, and the secretion of IL-1ß and IL-18. In addition, our data showed that TGF-ß1-treated liver cell conditional medium markedly induced HSC activation, which was rescued by YY1 knockdown in liver cells. YY1 overexpression in liver cells contributed to the activation of TGF-ß1-treated liver cell conditional medium in HSCs, however, this effect of YY1 was attenuated by NLRP3 inhibition. Overall, YY1 overexpression in liver cells contributed to HSC activation by facilitating IL-1ß and IL-18 production via activating NLRP3 inflammasome-mediated pyroptosis, thus aggravating hepatic fibrogenesis. Our data indicate that YY1 may be a novel target for the treatment of hepatic fibrosis and associated liver diseases.

Asunto(s)

Células Estrelladas Hepáticas; Inflamasomas; Cirrosis Hepática; Proteína con Dominio Pirina 3 de la Familia NLR; Piroptosis; Factor de Transcripción YY1; Animales; Factor de Transcripción YY1/metabolismo; Factor de Transcripción YY1/genética; Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo; Proteína con Dominio Pirina 3 de la Familia NLR/genética; Ratas; Inflamasomas/metabolismo; Cirrosis Hepática/patología; Cirrosis Hepática/metabolismo; Cirrosis Hepática/genética; Células Estrelladas Hepáticas/metabolismo; Células Estrelladas Hepáticas/patología; Masculino; Ratas Sprague-Dawley; Factor de Crecimiento Transformador beta1/metabolismo; Hígado/patología; Hígado/metabolismo; Interleucina-1beta/metabolismo

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Transcripción YY1 / Células Estrelladas Hepáticas / Inflamasomas / Piroptosis / Proteína con Dominio Pirina 3 de la Familia NLR / Cirrosis Hepática Límite: Animals Idioma: En Revista: Histol Histopathol Asunto de la revista: HISTOLOGIA / PATOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: España

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