S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis

Mazo, Daniel Ferraz de Campos; Oliveira, Marcelo Ganzarolli de; Pereira, Isabel Maria Teixeira Bicudo; Cogliati, Bruno; Stefano, José Tadeu; Souza, Gabriela Freitas Pereira de; Rabelo, Fabíola; Lima, Fábio; Alves, Venâncio Avancini Ferreira; Carrilho, Flair José; Oliveira, Cláudia Pinto Marques Souza de

doi:10.2147/dddt.s43930

Cited by 12 publications

(4 citation statements)

References 43 publications

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“…Yang et al reported that the expression of HSP60 was significantly upregulated in the liver tissue of mice with liver fibrosis and that this upregulation was reversed by a miR-29a mimic ( 49 ). Mazo et al also revealed that the expression of HSP60 mRNA was significantly increased in a rat model of nonalcoholic steatohepatitis, whereas S-nitroso-N-acetylcysteine decreased the expression of HSP60 and COL1A1 and alleviated liver fibrosis ( 50 ). HSP60 is mainly involved in protein transport and folding under physiological conditions.…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin inhibits the activation and proliferation of hepatic stellate cells by regulating miR‑29b‑3p

et al. 2023

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Liver fibrosis is an early pathological feature of hepatic diseases. Hepatic stellate cell (HSC) activation and disordered proliferation are associated with liver fibrosis. The present study identified significant differences in the expression levels of microRNA (miRNA/miR)-29b-3p in clinical samples and multiple miRNA databases. Subsequently, the specific antifibrotic mechanism of miR-29b-3p was further elucidated. Reverse transcription-quantitative PCR, western blot, ELISA and immunofluorescence were used to detect the expression levels of target genes and proteins. Oil red O, Nile red and trypan blue staining were used to evaluate HSC activation and cell viability. A luciferase assay was used to detect the relationship between miR-29b-3p and VEGFA. Adhesion, wound healing, apoptosis double staining and JC-1 assays were used to detect the effects of VEGFR1 and VEGFR2 knockdown on HSCs. Immunoprecipitation and fluorescence colocalization were used to identify interactions between the proteins. Furthermore, a rat fibrosis model was constructed to investigate the effects of dihydroartemisinin (DHA) and miR-29b-3p in vivo and in vitro . The results indicated that miR-29b-3p both inhibited the activation of HSCs and limited the proliferation of activated HSCs via lipid droplet recovery and VEGF pathway regulation. VEGFA was identified as a direct target of miR-29b-3p, and knockdown of VEGFA induced cell apoptosis and autophagy. Notably, VEGFR1 and VEGFR2 knockdown both promoted apoptosis; however, VEGFR1 knockdown inhibited autophagy, whereas VEGFR2 knockdown induced autophagy. Furthermore, it was revealed that VEGFR2 regulated autophagy by mediating the PI3K/AKT/mTOR/ULK1 pathway. VEGFR2 knockdown also led to ubiquitination of heat shock protein 60, ultimately inducing mitochondrial apoptosis. Finally, DHA was identified as a natural agonist of miR-29-3p that effectively prevented liver fibrosis in vivo and in vitro . Overall, the present study determined the molecular mechanism by which DHA inhibited HSC activation and prevented liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin inhibits the activation and proliferation of hepatic stellate cells by regulating miR‑29b‑3p

et al. 2023

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“…Hsp90 was found to regulate PPARγ activity in a mouse model of NAFLD, and its overexpression in cells could increase neutral lipid accumulation [ 5 ]. Previous studies have revealed that S-nitroso-N-acetylcysteine attenuated liver fibrosis in experimental non-alcoholic steatohepatitis via a mechanism that involved HSP60 downregulation [ 13 ]. HSP70, an informative representative of the HSP gene family, was recently found to be decreased in the liver and adipose tissue of obese patients.…”

Section: Discussionmentioning

confidence: 99%

Heat shock protein 70 promotes lipogenesis in HepG2 cells

Zhang¹,

Fan²,

Peng³

2018

Lipids Health Dis

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BackgroundThe increasing prevalence of non-alcoholic fatty liver disease (NAFLD) has followed the international rise in obesity rates. Multiple mechanisms are involved in NAFLD, including endoplasmic reticulum stress and oxidative stress. Heat shock protein 70 (HSP70), which is abundant in most organisms, is sensitive to stress. However, the role of HSP70 in NAFLD has not been investigated. Here, we investigated the possible role of HSP70 in lipid synthesis.MethodsC57BL/6 mice were fed a high-fat diet, and HepG2 cells were treated with 0.5 mM palmitic acid (PA). HSP70 expression was detected by qPCR, Western blot and immunohistochemistry. Total cholesterol (TC) and triglyceride (TG) levels were detected by enzyme-linked immunosorbent assay (ELISA). After Hsp70 overexpression and knockdown, TC and TG levels and FAS, SCD, and ACC expression were detected.ResultsHSP70 expression was significantly increased in the livers of obese mice. In vitro, HSP70 expression was markedly induced by PA in HepG2 cells. Notably, HSP70 overexpression in HepG2 cells enhanced TC and TG synthesis, in parallel with the upregulation of lipogenic genes, including FAS, SCD and ACC. By contrast, HSP70 knockdown decreased the levels of cellular lipids and the expression of FAS, SCD, and ACC in HepG2 cells. Together, our results suggest that HSP70 may promote lipogenesis in HepG2 cells.ConclusionsHeat shock protein 70 promotes lipogenesis in HepG2 cells.

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“…In the presence of macrophage infiltration, a pro-inflammatory state develops in visceral adipose tissue. Activation of TLR4 receptors in Kupffer cells and hepatocytes further activates and phosphorylates NF-κB, which induces cytokine and chemokine production by NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammatory vesicles (Mazo et al, 2013). These cytokines/chemokines accelerate the progression of non-alcoholic fatty liver to NASH by binding to specific receptors in the hepatocytes and immune response cells and then promoting inflammation and hepatocyte apoptosis.…”

Section: Potential Synergistic Mechanism Of Curcumin On the Transitio...mentioning

confidence: 99%

Protective role of curcumin in disease progression from non-alcoholic fatty liver disease to hepatocellular carcinoma: a meta-analysis

Li,

Deng,

Tan

et al. 2024

Front. Pharmacol.

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Background: Pathological progression from non-alcoholic fatty liver disease (NAFLD) to liver fibrosis (LF) to hepatocellular carcinoma (HCC) is a common dynamic state in many patients. Curcumin, a dietary supplement derived from the turmeric family, is expected to specifically inhibit the development of this progression. However, there is a lack of convincing evidence.Methods: The studies published until June 2023 were searched in PubMed, Web of Science, Embase, and the Cochrane Library databases. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) approach was used to evaluate the certainty of evidence. StataSE (version 15.1) and Origin 2021 software programs were used to analyze the critical indicators.Results: Fifty-two studies involving 792 animals were included, and three disease models were reported. Curcumin demonstrates a significant improvement in key indicators across the stages of NAFLD, liver fibrosis, and HCC. We conducted a detailed analysis of common inflammatory markers IL-1β, IL-6, and TNF-α, which traverse the entire disease process. The research results reveal that curcumin effectively hinders disease progression at each stage by suppressing inflammation. Curcumin exerted hepatoprotective effects in the dose range from 100 to 400 mg/kg and treatment duration from 4 to 10 weeks. The mechanistic analysis reveals that curcumin primarily exerts its hepatoprotective effects by modulating multiple signaling pathways, including TLR4/NF-κB, Keap1/Nrf2, Bax/Bcl-2/Caspase 3, and TGF-β/Smad3.Conclusion: In summary, curcumin has shown promising therapeutic effects during the overall progression of NAFLD–LF–HCC. It inhibited the pathological progression by synergistic mechanisms related to multiple pathways, including anti-inflammatory, antioxidant, and apoptosis regulation.

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S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis

Cited by 12 publications

References 43 publications

Dihydroartemisinin inhibits the activation and proliferation of hepatic stellate cells by regulating miR‑29b‑3p

Dihydroartemisinin inhibits the activation and proliferation of hepatic stellate cells by regulating miR‑29b‑3p

Heat shock protein 70 promotes lipogenesis in HepG2 cells

Protective role of curcumin in disease progression from non-alcoholic fatty liver disease to hepatocellular carcinoma: a meta-analysis

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