Histone methyltransferase SMYD2 regulates the activation of hepatic stellate cells by activating TLR4 signaling DOI Creative Commons
Kaize Ding,

Rujia Xie,

Bing Han

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 16, 2025

Liver fibrosis represents a pathological outcome in the progression of chronic liver diseases, primarily driven by activation hepatic stellate cells (HSCs) induced various injury factors. Substantial evidence indicates that under inflammatory conditions, aberrant HSCs leads to excessive deposition extracellular matrix (ECM). Therefore, identifying novel molecular targets inhibit and proliferation is significant clinical importance for prevention treatment fibrosis. SMYD2 (SET MYND domain containing 2) histone methyltransferase responsible catalyzing methylation lysine 36 on H3 (H3K36). However, specific role mechanisms remain poorly understood. Thus, this study aims systematically investigate regulatory development Our findings demonstrate both its catalytic product, H3K36me2, are significantly upregulated carbon tetrachloride (CCl4)-induced tissues mice during spontaneous primary mouse vitro. Knockdown expression reduces H3K36me2 modification levels effectively inhibits transforming growth factor-β1 (TGF-β1)-induced HSC activation. Further mechanistic studies reveal toll-like receptor 4 (TLR4) -nuclear factor kappa-B(NF-κB) signaling pathway involved process, where Smyd2 positively regulates Tlr4 gene modulating levels. These suggest may serve as potential therapeutic target fibrosis, warranting further exploration subsequent translational research.

Язык: Английский

Histone methyltransferase SMYD2 regulates the activation of hepatic stellate cells by activating TLR4 signaling DOI Creative Commons
Kaize Ding,

Rujia Xie,

Bing Han

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 16, 2025

Liver fibrosis represents a pathological outcome in the progression of chronic liver diseases, primarily driven by activation hepatic stellate cells (HSCs) induced various injury factors. Substantial evidence indicates that under inflammatory conditions, aberrant HSCs leads to excessive deposition extracellular matrix (ECM). Therefore, identifying novel molecular targets inhibit and proliferation is significant clinical importance for prevention treatment fibrosis. SMYD2 (SET MYND domain containing 2) histone methyltransferase responsible catalyzing methylation lysine 36 on H3 (H3K36). However, specific role mechanisms remain poorly understood. Thus, this study aims systematically investigate regulatory development Our findings demonstrate both its catalytic product, H3K36me2, are significantly upregulated carbon tetrachloride (CCl4)-induced tissues mice during spontaneous primary mouse vitro. Knockdown expression reduces H3K36me2 modification levels effectively inhibits transforming growth factor-β1 (TGF-β1)-induced HSC activation. Further mechanistic studies reveal toll-like receptor 4 (TLR4) -nuclear factor kappa-B(NF-κB) signaling pathway involved process, where Smyd2 positively regulates Tlr4 gene modulating levels. These suggest may serve as potential therapeutic target fibrosis, warranting further exploration subsequent translational research.

Язык: Английский

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