Therapeutic implications of targeting autophagy and TGF-β crosstalk for the treatment of liver fibrosis

被引：20

作者：

Siapoush, Samaneh ^{[1
]}

Rezaei, Ramazan ^{[1
]}

Alavifard, Helia ^{[1
]}

Hatami, Behzad ^{[2
]}

Zali, Mohammad Reza ^{[2
]}

Vosough, Massoud ^{[3
]}

Lorzadeh, Shahrokh ^{[4
]}

Los, Marek J. ^{[8
,9
]}

Baghaei, Kaveh ^{[1
,2
,10
]}

Ghavami, Saeid ^{[4
,5
,6
,7
,11
]}

机构：

[1] Shahid Beheshti Univ Med Sci, Res Inst Gastroenterol & Liver Dis, Basic & Mol Epidemiol Gastrointestinal Disorders R, Tehran, Iran

[2] Shahid Beheshti Univ Med Sci, Res Inst Gastroenterol & Liver Dis, Gastroenterol & Liver Dis Res Ctr, Tehran, Iran

[3] ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Regenerat Med, Tehran, Iran

[4] Univ Manitoba, Max Rady Coll Med, Rady Fac Hlth Sci, Dept Human Anat & Cell Sci, Winnipeg, MB, Canada

[5] Univ Technol Katowice, Fac Med Zabrze, PL-41800 Zabrze, Poland

[6] Canc Care Manitoba Univ Manitoba, Res Inst Oncol & Hematol, Winnipeg, MB, Canada

[7] Univ Manitoba, Dept Human Anat & Cell Sci, Coll Med, Winnipeg, MB, Canada

[8] Silesian Tech Univ, Biotechnol Ctr, 8 Krzywousty St, PL-44100 Gliwice, Poland

[9] Shiraz Univ Med Sci, Autophagy Res Ctr, Dept Biochem, Shiraz, Iran

[10] Shahid Beheshti Univ Med Sci, Res Inst Gastroenterol & Liver Dis RIGLD, Aerabi St, Yemen St, Chamran Highway, Tehran, Iran

[11] Univ Manitoba, Max Rady Coll Med, Rady Fac Hlth Sci, Dept Human Anat & Cell Sci, Winnipeg, MB, Canada

来源：

LIFE SCIENCES | 2023年 / 329卷

关键词：

Lipophagy; Hepatocyte; Hepatocellular Carcinoma; Extracellular matrix; HEPATIC STELLATE CELLS; NF-KAPPA-B; SIGNALING PATHWAY; LIPID DROPLETS; INHIBITION; ACTIVATION; APOPTOSIS; INJURY; PROTECTS; MATRIX;

D O I：

10.1016/j.lfs.2023.121894

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Liver fibrosis is characterized by the excessive deposition and accumulation of extracellular matrix components, mainly collagens, and occurs in response to a broad spectrum of triggers with different etiologies. Under stress conditions, autophagy serves as a highly conserved homeostatic system for cell survival and is importantly involved in various biological processes. Transforming growth factor-& beta;1 (TGF-& beta;1) has emerged as a central cytokine in hepatic stellate cell (HSC) activation and is the main mediator of liver fibrosis. A growing body of evidence from preclinical and clinical studies suggests that TGF-& beta;1 regulates autophagy, a process that affects various essential (patho)physiological aspects related to liver fibrosis. This review comprehensively highlights recent advances in our understanding of cellular and molecular mechanisms of autophagy, its regulation by TGF & beta;, and the implication of autophagy in the pathogenesis of progressive liver disorders. Moreover, we evaluated crosstalk between autophagy and TGF-& beta;1 signalling and discussed whether simultaneous inhibition of these pathways could represent a novel approach to improve the efficacy of anti-fibrotic therapy in the treatment of liver fibrosis.

引用

页数：15

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