Taurine ameliorates liver fibrosis by repressing Fpr2-regulated macrophage M1 polarization

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177614 - 177614

Опубликована: Апрель 1, 2025

Liver fibrosis is a reversible pathophysiological condition characterized by excessive extracellular matrix deposition that can progress to cirrhosis and liver failure if left untreated. Taurine, sulfur-containing amino acid, protects the from damage. However, effects of taurine on fibrogenesis have not been completely elucidated. In this study, we used acid metabolomics, gene expression microanalysis, single-cell RNA sequencing (scRNA-seq) investigate roles taurine, formyl peptide receptor 2 (Fpr2), proinflammatory macrophages in human fibrotic sections two distinct mouse models fibrosis. Taurine transporter SLC6A6 wild-type knockout littermate critical element inhibitors were also used. We found levels significantly reduced both murine exogenous supplementation alleviated via SLC6A6. Furthermore, microarray analysis scRNA-seq analyses demonstrated mitigated fibrosis, mainly regulating Fpr2-related macrophage status. WRW4-mediated inhibition Fpr2 ameliorated M1 polarization Additionally, suppressed Fpr2-modulated production associated cytokines repressing NF-κBp65 phosphorylation; moreover, deficiency or treatment with an NF-κB inhibitor, BAY, impaired protective effect taurine. Therefore, exerts against Fpr2/NF-κBp65-regulated polarization, highlighting its potential therapeutic agent.

Язык: Английский

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Mitochondrial dysfunction induced by HIF‐1α under hypoxia contributes to the development of gastric mucosal lesions

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(4)

Опубликована: Апрель 1, 2024

Abstract Introduction Hypoxia is an important characteristic of gastric mucosal diseases, and hypoxia‐inducible factor‐1α (HIF‐1α) contributes to microenvironment disturbance metabolic spectrum abnormalities. However, the underlying mechanism HIF‐1α its association with mitochondrial dysfunction in lesions under hypoxia have not been fully clarified. Objectives To evaluate effects hypoxia‐induced on development lesions. Methods Portal hypertensive gastropathy (PHG) cancer (GC) were selected as representative diseases benign malignant lesions, respectively. Gastric tissues from patients diagnosed above collected. hypertension (PHT)‐induced mouse models METTL3 mutant or NLRP3 ‐deficient littermates established, nude graft tumour relevant inhibitors generated. The mechanisms hypoxic condition, alterations further analysed. Results HIF‐1α, which can mediate via upregulation METTL3/IGF2BP3‐dependent dynamin‐related protein 1 (Drp1) N6‐methyladenosine modification increase reactive oxygen species (mtROS) production, was elevated conditions human portal mucosa GC tissues. While blocking PX‐478, inhibiting Drp1‐dependent fission division inhibitor (Mdivi‐1) treatment mutation alleviated this process. Furthermore, influenced energy metabolism by enhancing glycolysis lactate dehydrogenase A. In addition, HIF‐1α‐induced also enhanced glycolysis. associated antioxidant enzyme activity electron transport chain, resulting massive mtROS needed for activation inflammasome aggravate PHG GC. Conclusions Under conditions, enhances influences profile altering trigger contribute

Язык: Английский

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Molecular mechanism of portal hypertensive gastropathy: An update

Clinics and Research in Hepatology and Gastroenterology, Год журнала: 2024, Номер 48(8), С. 102423 - 102423

Опубликована: Июль 19, 2024

Язык: Английский

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