PMID- 27881436 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 2046-6390 (Print) IS - 2046-6390 (Electronic) IS - 2046-6390 (Linking) VI - 6 IP - 1 DP - 2017 Jan 15 TI - Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver fibrosis by inhibiting the activation of hepatic stellate cells. PG - 29-34 LID - 10.1242/bio.019828 [doi] AB - 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-beta treatment increased alpha-SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced alpha-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. CI - (c) 2017. Published by The Company of Biologists Ltd. FAU - Liu, Jingmei AU - Liu J AD - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Li, Mengke AU - Li M AD - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - Department of Gastroenterology, Zhoushan Hospital, Zhoushan 316000, China. FAU - Gong, Jin AU - Gong J AD - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Han, Ping AU - Han P AD - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Wang, Yunwu AU - Wang Y AD - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Li, Dongxiao AU - Li D AD - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Tian, Dean AU - Tian D AUID- ORCID: 0000-0002-1407-6351 AD - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China datian@tjh.tjmu.edu.cn liaojiazhi2011@163.com. FAU - Liao, Jiazhi AU - Liao J AD - Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China datian@tjh.tjmu.edu.cn liaojiazhi2011@163.com. LA - eng PT - Journal Article DEP - 20170115 PL - England TA - Biol Open JT - Biology open JID - 101578018 PMC - PMC5278420 OTO - NOTNLM OT - ER stress OT - HRC OT - Hepatic stellate cells OT - Liver fibrosis COIS- The authors declare no competing or financial interests. EDAT- 2016/11/25 06:00 MHDA- 2016/11/25 06:01 PMCR- 2016/11/23 CRDT- 2016/11/25 06:00 PHST- 2016/11/25 06:00 [pubmed] PHST- 2016/11/25 06:01 [medline] PHST- 2016/11/25 06:00 [entrez] PHST- 2016/11/23 00:00 [pmc-release] AID - bio.019828 [pii] AID - BIO019828 [pii] AID - 10.1242/bio.019828 [doi] PST - epublish SO - Biol Open. 2017 Jan 15;6(1):29-34. doi: 10.1242/bio.019828.