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

Sun,Yimin; Liu,Bingyan; Xie,Jianping; Jiang,Xuefeng; Xiao,Baolai; Hu,Xiaomiao; Xiang,Jinjian

doi:10.3892/mmr.2022.12697

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

Authors:
- Yimin Sun
- Bingyan Liu
- Jianping Xie
- Xuefeng Jiang
- Baolai Xiao
- Xiaomiao Hu
- Jinjian Xiang
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Affiliations: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434000, P.R. China, Department of Neurology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434000, P.R. China
Published online on: March 23, 2022 https://doi.org/10.3892/mmr.2022.12697
Article Number: 181
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aspirin reduces the liver fibrosis index and inflammation in patients and rats. However, the specific mechanism underlying the effects of aspirin are yet to be elucidated. The present study aimed to investigate the effects of aspirin on thioacetamide (TAA)‑induced liver fibrosis in rats and hepatic stellate cells (HSCs) via the TGF‑β1/Smad signaling pathway. Liver fibrosis was induced in Sprague Dawley rats by intraperitoneal injection of 200 mg/kg TAA twice weekly for 8 weeks. Aspirin (30 mg/kg) was administered to rats by gavage once every morning over a period of 8 weeks. Masson's trichrome and H&E staining were used to detect and analyze the pathological changes in liver tissues. Western blot analysis and immunohistochemistry were applied to determine the protein expression levels of α‑smooth muscle actin (α‑SMA), collagen I, TGF‑β1, phosphorylated (p)‑Smad2 and p‑Smad3. In addition, reverse transcription‑quantitative PCR was performed to detect the mRNA expression levels of α‑SMA, collagen type I α 1 chain (COL1A1) and TGF‑β1. The results demonstrated that treatment with aspirin significantly reduced the serum levels of alanine aminotransferase, aspartate aminotransferase and hydroxyproline in the TAA + aspirin compared with that in the TAA group. In the rat liver fibrosis model, pathological changes in liver tissues were improved following treatment with aspirin. Similarly, a marked decrease was observed in protein expression levels of α‑SMA, collagen I, TGF‑β1, p‑Smad2 and p‑Smad3. Furthermore, aspirin administration decreased the mRNA levels of α‑SMA, COL1A1 and TGF‑β1. In addition, HSCs were treated with different concentrations of aspirin (10, 20 and 40 mmol/l), and the protein expression levels of α‑SMA, collagen I, TGF‑β1, p‑Smad2 and p‑Smad3 were reduced in a dose‑dependent manner. Overall, the present study showed that aspirin attenuated liver fibrosis and reduced collagen production by suppressing the TGF‑β1/Smad signaling pathway, thus revealing a potential mechanism of aspirin in the treatment of liver fibrosis.

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