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Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells

The histidine-rich calcium-binding protein (HRC) is a regulator of Ca(2+) homeostasis and it plays a significant role in hepatocellular carcinoma (HCC) progression. However, the relationship between HRC and liver fibrogenesis is still unknown. Our data demonstrates that HRC was upregulated in fibrot...

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Detalles Bibliográficos
Autores principales: Liu, Jingmei, Li, Mengke, Gong, Jin, Han, Ping, Wang, Yunwu, Li, Dongxiao, Tian, Dean, Liao, Jiazhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278420/
https://www.ncbi.nlm.nih.gov/pubmed/27881436
http://dx.doi.org/10.1242/bio.019828
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author Liu, Jingmei
Li, Mengke
Gong, Jin
Han, Ping
Wang, Yunwu
Li, Dongxiao
Tian, Dean
Liao, Jiazhi
author_facet Liu, Jingmei
Li, Mengke
Gong, Jin
Han, Ping
Wang, Yunwu
Li, Dongxiao
Tian, Dean
Liao, Jiazhi
author_sort Liu, Jingmei
collection PubMed
description The histidine-rich calcium-binding protein (HRC) is a regulator of Ca(2+) homeostasis and it plays a significant role in hepatocellular carcinoma (HCC) progression. However, the relationship between HRC and liver fibrogenesis is still unknown. Our data demonstrates that HRC was upregulated in fibrotic liver and activated hepatic stellate cells (HSCs). TGF-β treatment increased α-SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced α-SMA, CTGF and collagen expression, and inhibited HSC proliferation and migration. In addition, we found that the anti-fibrosis effect of HRC knockdown was associated with endoplasmic reticulum (ER) stress. Silencing of HRC decreased the expression of ER stress and autophagy markers. Moreover, ER stress agonist thapsigargin (TG) enhanced, whereas ER stress antagonist 4-phenylbutyric acid (4-PBA) alleviated HSCs activation and autophagy. In conclusion, these data indicate that depletion of HRC inhibited HSC activation through the ER stress pathway, and HRC may be a potential regulator of liver fibrosis.
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spelling pubmed-52784202017-02-13 Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells Liu, Jingmei Li, Mengke Gong, Jin Han, Ping Wang, Yunwu Li, Dongxiao Tian, Dean Liao, Jiazhi Biol Open Research Article The histidine-rich calcium-binding protein (HRC) is a regulator of Ca(2+) homeostasis and it plays a significant role in hepatocellular carcinoma (HCC) progression. However, the relationship between HRC and liver fibrogenesis is still unknown. Our data demonstrates that HRC was upregulated in fibrotic liver and activated hepatic stellate cells (HSCs). TGF-β treatment increased α-SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced α-SMA, CTGF and collagen expression, and inhibited HSC proliferation and migration. In addition, we found that the anti-fibrosis effect of HRC knockdown was associated with endoplasmic reticulum (ER) stress. Silencing of HRC decreased the expression of ER stress and autophagy markers. Moreover, ER stress agonist thapsigargin (TG) enhanced, whereas ER stress antagonist 4-phenylbutyric acid (4-PBA) alleviated HSCs activation and autophagy. In conclusion, these data indicate that depletion of HRC inhibited HSC activation through the ER stress pathway, and HRC may be a potential regulator of liver fibrosis. The Company of Biologists Ltd 2016-11-23 /pmc/articles/PMC5278420/ /pubmed/27881436 http://dx.doi.org/10.1242/bio.019828 Text en © 2017. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Liu, Jingmei
Li, Mengke
Gong, Jin
Han, Ping
Wang, Yunwu
Li, Dongxiao
Tian, Dean
Liao, Jiazhi
Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells
title Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells
title_full Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells
title_fullStr Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells
title_full_unstemmed Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells
title_short Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells
title_sort knockdown of histidine-rich calcium-binding protein (hrc) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278420/
https://www.ncbi.nlm.nih.gov/pubmed/27881436
http://dx.doi.org/10.1242/bio.019828
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