Endostatin attenuates PDGF-BB- or TGF-β1-induced HSCs activation via suppressing RhoA/ROCK1 signal pathways
Open Access
- 1 January 2019
- journal article
- research article
- Published by Taylor & Francis Ltd in Drug Design, Development and Therapy
- Vol. ume 13, 285-290
- https://doi.org/10.2147/dddt.s191617
Abstract
Aim: To testify the hypothesis that endostatin exerts antifibrotic effects in hepatic stellate cells (HSCs) by modulating RhoA (ras homolog gene family, member A)/ROCK 1 (Rho-associated protein kinase 1) signal pathways. Materials and methods: HSCs-T6 of passages 3–5 were cultured in DMEM and serum starved for 48 hours. HSCs were grouped as follows: control group, TGF-β1 (transforming growth factor β1) group, endostatin+TGF-β1 group, PDGF-BB (platelet-derived growth factor-BB) group, and endostatin+PDGF-BB group. In the PDGF-BB group, HSCs were treated with PDGF-BB (200 ng/mL) for 72 hours; in the TGF-β1 group, they were treated with TGF-β1 (10 ng/mL) for 72 hours. In the Endostatin+TGF-β1 group or Endostatin+PDGF-BB group, HSCs were treated with TGF-β1 (10 ng/mL) or PDGF-BB (200 ng/mL) for 72 hours after pretreatment with endostatin (5 µg/mL) for 1 hour. In the control group, HSCs were only treated with serum-free DMEM for 72 hours. Collagen I was analyzed with ELISA. F-actin was detected with immunofluorescent staining. The mRNAs and proteins of α-smooth muscle actin, RhoA, and ROCK1 were analyzed by using real-time PCR and Western blot, respectively. Results: TGF-β1 and PDGF-BB promote the proliferation of HSCs significantly at 48 and 72 hours. Endostatin inhibits the proliferation effect induced by TGF-β1 or PDGF-BB significantly (PPPPConclusion: These results suggested that endostatin inhibited TGF-β1- or PDGF-BB-induced fibrosis in HSCs by modulating RhoA/ROCK signal pathways.Keywords
This publication has 19 references indexed in Scilit:
- ANGIOGENESIS INHIBITOR ENDOSTATIN PROTECTS MICE WITH SEPSIS FROM MULTIPLE ORGAN DYSFUNCTION SYNDROMEShock, 2015
- Human recombinant endostatin Endostar attenuates hepatic sinusoidal endothelial cell capillarization in CCl4-induced fibrosis in miceMolecular Medicine Reports, 2015
- Pericyte-endothelial crosstalk: implications and opportunities for advanced cellular therapiesTranslational Research, 2014
- Origins of fibrosis: pericytes take centre stageF1000Prime Reports, 2013
- Recruitment and retention: factors that affect pericyte migrationCellular and Molecular Life Sciences, 2013
- Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in ratsRespiratory Research, 2013
- Endostatin inhibits hypertrophic scarring in a rabbit ear modelJournal of Zhejiang University-SCIENCE B, 2013
- Update on hepatic stellate cells: pathogenic role in liver fibrosis and novel isolation techniquesExpert Review of Gastroenterology & Hepatology, 2012
- Rho kinase-1 mediates cardiac fibrosis by regulating fibroblast precursor cell differentiationCardiovascular Research, 2009
- The Global Impact of Hepatic Fibrosis and End-Stage Liver DiseaseClinics in Liver Disease, 2008