Fluorofenidone affects hepatic stellate cell activation in hepatic fibrosis by targeting the TGF‑β1/Smad and MAPK signaling pathways

Peng,Yu; Li,Li; Zhang,Xin; Xie,Mingyan; Yang,Congying; Tu,Sha; Shen,Hong; Hu,Gaoyun; Tao,Lijian; Yang,Huixiang

doi:10.3892/etm.2019.7548

Fluorofenidone affects hepatic stellate cell activation in hepatic fibrosis by targeting the TGF‑β1/Smad and MAPK signaling pathways

Authors:
- Yu Peng
- Li Li
- Xin Zhang
- Mingyan Xie
- Congying Yang
- Sha Tu
- Hong Shen
- Gaoyun Hu
- Lijian Tao
- Huixiang Yang
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Affiliations: Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Gastroenterology, The First People's Hospital of Changde City, Changde, Hunan 415000, P.R. China, Department of General Practice, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu 222000, P.R. China, Department of Endoscopy Center, Hunan Cancer Hospital, Changsha, Hunan 410000, P.R. China, Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China, Faculty of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410000, P.R. China, Department of Nephropathy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: May 6, 2019 https://doi.org/10.3892/etm.2019.7548
Pages: 41-48
Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present research was to study the therapeutic impacts of fluorofenidone (AKF‑PD) on pig serum (PS)‑induced liver fibrosis in rats and the complex molecular mechanisms of its effects on hepatic stellate cells (HSCs). Wistar rats were randomly divided into normal control, PS and PS/AKF‑PD treatment groups. The activated human HSC LX‑2 cell line was also treated with AKF‑PD. The expression of collagen I and III, and α‑smooth muscle actin (α‑SMA) was determined by immunohistochemical staining and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Western blotting and/or RT‑qPCR analyses were used to determine the expression of transforming growth factor (TGF)‑β1, α‑SMA, collagen I, mothers against decapentaplegic homolog (Smad)‑3, extracellular signal‑regulated kinase (ERK)1/2, p38 mitogen‑activated protein kinase (p38 MAPK) and c‑Jun N‑terminal kinase (JNK). AKF‑PD attenuated the degree of hepatic fibrosis and liver injury in vivo, which was associated with the downregulation of collagen I and III, and α‑SMA at the mRNA and protein levels. In vitro, AKF‑PD treatment significantly reduced the TGF‑β1‑induced activation of HSCs, as determined by the reduction in collagen I and α‑SMA protein expression. The TGF‑β1‑induced upregulation of the phosphorylation of Smad 3, ERK1/2, p38 and JNK was attenuated by AKF‑PD treatment. These findings suggested that AKF‑PD attenuated the progression of hepatic fibrosis by suppressing HSCs activation via the TGF‑β1/Smad and MAPK signaling pathways, and therefore that AKF‑PD may be suitable for use as a novel therapeutic agent against liver fibrosis.

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