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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
Published on: May 3, 2024
Transcription factor YY1 accelerates hepatic fibrosis development by activating NLRP3 inflammasome-mediated
Xiao Fu1, Ping Xiao1, Xin Luo1
1General Medicine Department, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, PR China.
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-β1-treated liver cells. In animal experiments, YY1 knockdown effectively attenuated CCl4-induced liver injury and pyroptosis-related IL-1β and IL-18 expression. In cellular experiments, NLRP3 inflammasome-mediated pyroptosis was activated by TGF-β1 treatment, while YY1 knockdown significantly inhibited the activation of the NLRP3 inflammasome, pyroptosis, and the secretion of IL-1β and IL-18. In addition, our data showed that TGF-β1-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-β1-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-1β 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.
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