Interaction between insulin-like growth factor binding protein-related protein 1 and transforming growth factor beta 1 in primary hepatic stellate cells
Xiu-Qing Li, Qian-Qian Zhang, Hai-Yan Zhang, Xiao-Hong Guo, Hui-Qin Fan and Li-Xin Liu
Taiyuan, China
Author Affiliations: Department of Gastroenterology and Hepatology (Li XQ, Zhang QQ, Zhang HY, Guo XH, Fan HQ and Liu LX), Experimental Center of Science and Research (Zhang QQ, Zhang HY, Guo XH, Fan HQ and Liu LX), The First Clinical Hospital of Shanxi Medical University; and Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Shanxi Medical University (Zhang QQ, Zhang HY, Guo XH, Fan HQ and Liu LX), Taiyuan 030001, China
Corresponding Author: Li-Xin Liu, MD, PhD, Department of Gastroenterology and Hepatology and Experimental Center of Science and Research, The First Clinical Hospital of Shanxi Medical University; and Key Laboratory of Cell Physiology, Provincial Department of the Ministry of Education, Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030001, China (Tel: +86-351-4639075; Fax: +86-351-8263169; Email: lixinliu6@hotmail.com)
Abstract：BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGFβ1) is known as the strongest effector of liver fibrosis. Therefore, we aimed to investigate the detailed interaction between IGFBPrP1 and TGFβ1 in primary hepatic stellate cells (HSCs).
METHODS: We overexpressed TGFβ1 or IGFBPrP1 and inhibited TGFβ1 expression in primary HSCs for 6, 12, 24, 48, 72, and 96 hours to investigate their interaction and observe the accompanying expressions of α-smooth muscle actin (α-SMA), collagen I, fibronectin, and phosphorylated-mothers against decapentaplegic homolog 2/3 (p-Smad2/3).
RESULTS: We found that the adenovirus vector encoding the TGFβ1 gene (AdTGFβ1) induced IGFBPrP1 expression while that of α-SMA, collagen I, fibronectin, and TGFβ1 increased gradually. Concomitantly, AdIGFBPrP1 upregulated TGFβ1, α-SMA, collagen I, fibronectin, and p-Smad2/3 in a time-dependent manner while IGFBPrP1 expression was decreased at 96 hours. Inhibition of TGFβ1 expression reduced the IGFBPrP1-stimulated expression of α-SMA, collagen I, fibronectin, and p-Smad2/3.
CONCLUSIONS: These findings for the first time suggest the existence of a possible mutually regulation between IGFBPrP1 and TGFβ1, which likely accelerates liver fibrosis progression. Furthermore, IGFBPrP1 likely participates in liver fibrosis in a TGFβ1-depedent manner, and may act as an upstream regulatory factor of TGFβ1 in the Smad pathway.
2017, Vol. 16 
