Aspirin attenuates liver fibrosis by suppressing TGF‑β1/Smad signaling

Sun, Yimin; Liu, Bingyan; Xie, Jianping; Jiang, Xuefeng; Xiao, Bao-Lai; Hu, Xiaomiao; Xiang, Jinjian

doi:10.3892/mmr.2022.12697

Cited by 26 publications

(18 citation statements)

References 39 publications

(38 reference statements)

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“…The excessive generation and deposition of these two molecules form the principal scaffold of the fibrotic scar tissue. The expression levels and deposition of Collagen I, due to their strong correlation with the extent of fibrosis and the pace of disease progression, are widely employed as critical yardsticks for gauging the depth and velocity of the fibrotic process [35,36]. Concurrently, Collagen III assumes a non-negligible role in the early stages of liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Resveratrol on Cytotoxicity of Mouse Hepatic Stellate Cells Induced by PM2.5

Zhang,

Chen,

Bai

et al. 2024

Atmosphere

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The atmosphere’s fine particulate matter (PM2.5) can enter the liver through the circulatory system, leading to hepatic inflammation and fibrosis. As a non-flavonoid polyphenolic compound, resveratrol (RES) has anti-oxidant, anti-inflammatory and hepatoprotective effects, but the molecular mechanisms of liver fibrosis induced by PM2.5 exposure are still limited. In this study, we established an in vitro cell model to investigate the intervention effect of RES with different concentrations (5 and 20 μmol/mL) on mouse hepatic stellate cells (mHSCs) injury induced by PM2.5 (100 μg/mL). We determined the cell viability in mHSCs after treatment with PM2.5 or/and RES for 24 h. We investigated the intracellular oxidative stress by detecting the changes in reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) levels. We also measured the protein expressions of fibrosis-related genes (α-SMA, Collagen I and Collagen III) and key genes (SIRT1, NF-κB, NLRP3, Cleaved-Caspase1, IL-1β) in the NLRP3 pathway in mHSCs exposed to PM2.5 with or without RES. The results showed that (1) PM2.5 has cytotoxic effects on mHSCs, whereas RES (5 μmol/L and 20 μmol/L) inhibited PM2.5-induced cytotoxicity and LDH leakage; (2) RES effectively reduces ROS and MDA production caused by PM2.5 while concurrently enhancing SOD levels, thereby improving cellular anti-oxidant capacity; (3) the expression of α-SMA, Collagen I and Collagen III were notably downregulated in the PM2.5 plus RES treatment group compared to the PM2.5-exposed group; (4) RES significantly increased SIRT1 expression and decreased the expression of NF-κB, NLRP3, Cleaved-Caspase1 and IL-1β in mHSCs exposure to PM2.5 compared to the PM2.5 group. These results demonstrate that RES can up-regulate SIRT1 and mitigate PM2.5-induced fibrosis by suppressing oxidative stress in mHSCs and the SIRT1/NF–κB/NLRP3 pathway activated by PM2.5.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Resveratrol on Cytotoxicity of Mouse Hepatic Stellate Cells Induced by PM2.5

Zhang,

Chen,

Bai

et al. 2024

Atmosphere

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“…Therefore, early intervention decreases risk of progression to end-stage liver disease (3,4). Although almost all types of chronic liver diseases (chemically toxic, infectious, genetic/metabolic, autoimmune) can lead to liver fibrosis, the mechanisms of liver fibrosis are still not fully understood (5,6). The successful treatment of liver fibrosis remains unsatisfactory with cytokine analogs, antioxidants and other drugs (7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…To the best of our knowledge, only Sun et al ( 6 ) have reported the effect of aspirin on liver fibrosis via inhibition of the TGFβ1/SMAD pathway. Aspirin has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis ( 19 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

“…Aspirin has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis ( 19 , 20 ). More studies are needed to determine the protective effect of aspirin in liver fibrosis models and its potential mechanisms ( 6 ). Here, to explore the effect of aspirin on liver fibrosis, a hepatic fibrosis rat model induced by CCl 4 was used and evaluated following aspirin treatment.…”

Section: Introductionmentioning

confidence: 99%

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The hepatoprotective effect of aspirin on carbon tetrachloride‑induced hepatic fibrosis via inhibition of TGFβ‑1 pathway and pro‑inflammatory cytokines IL‑1β and COX‑2 in rats

Zhong

et al. 2023

Exp Ther Med

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Aspirin decreases liver fibrosis index and inflammation levels. However, the exact mechanism underlying the effects of aspirin are yet to be elucidated. The aim of the study was to investigate the potential protective effects of aspirin on carbon tetrachloride (CCl 4 )-induced hepatic fibrosis in Sprague-Dawley rats. Rats were divided into four groups, including healthy and CCl 4 control and low-(aspirin 10 mg/kg + CCl 4 ) and high-dose aspirin group (aspirin 300 mg/kg + CCl 4 ). After 8 weeks treatment, the histopathological examinations of hepatocyte fibrosis in liver and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-1β, transforming growth factor-β1 (TGF-β1), hyaluronic acid (HA), laminin (LN) and type IV collagen (IV.C) were determined. Histopathological examination suggested that aspirin decreased CCl 4 -induced hepatic fibrosis and liver inflammation. The high-dose aspirin group significantly decreased the serum levels of ALT, AST, HA and LN compared with the CCl 4 control group. High-dose aspirin group significantly decreased the levels of pro-inflammatory cytokines IL-1β compared with CCl 4 group. The high-dose aspirin group significantly inhibited the expression of TGFβ-1 protein compared with CCl 4 group. Overall, the present study indicated that aspirin exhibited potent protective effects against CCl 4 -induced hepatic fibrosis via inhibition of the TGFβ-1 pathway and pro-inflammatory cytokine IL-1β.

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“…Sun, Liu [ 98 ] found that in the liver fibrosis model of rats, aspirin improved the degenerative abnormalities in the liver tissues. In a cross-sectional analysis, aspirin use was associated with significantly lower indicators of liver fibrosis in US individuals with suspected chronic liver diseases [ 99 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting HSP47 and HSP70: promising therapeutic approaches in liver fibrosis management

El-Fattah

Zakaria

2022

J Transl Med

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Liver fibrosis is a liver disease in which there is an excessive buildup of extracellular matrix proteins, including collagen. By regulating cytokine production and the inflammatory response, heat shock proteins (HSPs) contribute significantly to a wider spectrum of fibrotic illnesses, such as lung, liver, and idiopathic pulmonary fibrosis by aiding in the folding and assembly of freshly synthesized proteins, HSPs serve as chaperones. HSP70 is one of the key HSPs in avoiding protein aggregation which induces its action by sending unfolded and/or misfolded proteins to the ubiquitin–proteasome degradation pathway and antagonizing influence on epithelial-mesenchymal transition. HSP47, on the other hand, is crucial for boosting collagen synthesis, and deposition, and fostering the emergence of fibrotic disorders. The current review aims to provide light on how HSP70 and HSP47 affect hepatic fibrogenesis. Additionally, our review looks into new therapeutic approaches that target HSP70 and HSP47 and could potentially be used as drug candidates to treat liver fibrosis, especially in cases of comorbidities.

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Aspirin attenuates liver fibrosis by suppressing TGF‑β1/Smad signaling

Cited by 26 publications

References 39 publications

Protective Effects of Resveratrol on Cytotoxicity of Mouse Hepatic Stellate Cells Induced by PM2.5

Protective Effects of Resveratrol on Cytotoxicity of Mouse Hepatic Stellate Cells Induced by PM2.5

The hepatoprotective effect of aspirin on carbon tetrachloride‑induced hepatic fibrosis via inhibition of TGFβ‑1 pathway and pro‑inflammatory cytokines IL‑1β and COX‑2 in rats

Targeting HSP47 and HSP70: promising therapeutic approaches in liver fibrosis management

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