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Endoplasmic reticulum stress is the crossroads of autophagy, inflammation, and apoptosis signaling pathways and participates in liver fibrosis

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Abstract

Objective

The objective of the review is to examine the crossroads of autophagy, inflammation, and apoptosis signaling pathways and their participation in liver fibrosis.

Introduction

Endoplasmic reticulum (ER) stress was emerged as a common feature relevant to the pathogenesis of diseases associated with organ fibrosis. However, the functional consequences of these alterations on ER stress and the possible involvement in liver fibrosis were currently largely unexplored. Here, we will survey the recent literature in the field and discuss recent insights focusing on some cellular models expressing mutant proteins involved in liver fibrosis.

Methods

A computer-based online search with PubMed, Scopus and Web of Science databases was performed for articles published, concerning ER stress, adaptation, inflammation and apoptosis with relevance to liver fibrosis.

Results and conclusions

Progression of liver fibrosis requires sustained inflammation leading to hepatocytes apoptosis through ER stress, whereas associated with activation of hepatic stellate cells (HSCs) into a fibrogenic and proliferative cell type. Faced with persistent and massive ER stress, HSCs adaptation starts to fail and apoptosis occurs in reversal of liver fibrosis, possibly mediated through calcium perturbations, unfolded protein response, and the pro-apoptotic transcription factor CHOP. Although limited in scope, current studies underscored that ER stress is tightly linked to adaptation, inflammation and apoptosis, and recent evidences suggested that these processes are related to the pathogenesis of liver fibrosis and its recovery.

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Acknowledgments

This study is supported by the Chinese National Natural Science Foundation Project (No. 81102493, 81273526, 81072686) and the Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20103420120001).

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Authors and Affiliations

  1. Department of Pharmacy, The People’s Hospital of Bozhou, Bozhou, 236800, China

    Xiaohui Li

  2. School of Pharmacy, Anhui Medical University, Hefei, Anhui, China, 230032

    Xiaohui Li, Yarui Wang, Huan Wang, Cheng Huang, Yan Huang & Jun Li

  3. Institute for Liver Diseases, Anhui Medical University, Hefei, 230032, China

    Xiaohui Li, Yarui Wang, Huan Wang, Cheng Huang, Yan Huang & Jun Li

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  1. Xiaohui Li
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  2. Yarui Wang
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  3. Huan Wang
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  4. Cheng Huang
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  5. Yan Huang
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  6. Jun Li
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Correspondence to Yan Huang or Jun Li.

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Li, X., Wang, Y., Wang, H. et al. Endoplasmic reticulum stress is the crossroads of autophagy, inflammation, and apoptosis signaling pathways and participates in liver fibrosis. Inflamm. Res. 64, 1–7 (2015). https://doi.org/10.1007/s00011-014-0772-y

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  • DOI: https://doi.org/10.1007/s00011-014-0772-y

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