Endostatin attenuates PDGF-BB- or TGF-β1-induced HSCs activation via suppressing RhoA/ROCK1 signal pathways
Haitao Ren,1 Yuan Li,2 Yan Chen,3 Liang Wang4 1Department of Burns and Wound Care Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China; 2Department of Ultrasound, Women’s Hospital, School of Medicine, Zhejiang University, H...
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doaj-34c87ab85ac3478b8d453503306f92882020-11-25T00:29:41ZengDove Medical PressDrug Design, Development and Therapy1177-88812019-01-01Volume 1328529043520Endostatin attenuates PDGF-BB- or TGF-β1-induced HSCs activation via suppressing RhoA/ROCK1 signal pathwaysRen HLi YChen YWang LHaitao Ren,1 Yuan Li,2 Yan Chen,3 Liang Wang4 1Department of Burns and Wound Care Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China; 2Department of Ultrasound, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China; 3Emergency Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China; 4Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China 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 (P<0.01). The expression of collagen I and F-actin was significantly upregulated in both TGF-β1 and PDGF-BB groups than in the control group (P<0.01). Both the collagen I and F-actin expression were downregulated significantly in the endostatin-treated groups (P<0.05). Endostatin significantly inhibited the upregulated expression of α-smooth muscle actin, RhoA, and ROCK1 induced by TGF-β1 or PDGF-BB (P<0.01).Conclusion: These results suggested that endostatin inhibited TGF-β1- or PDGF-BB-induced fibrosis in HSCs by modulating RhoA/ROCK signal pathways.Keywords: endostatin, liver fibrogenesis, hepatic stellate cell, signal pathways, fibrosis https://www.dovepress.com/endostatin-attenuates-pdgf-bb--or-tgf-beta1-induced-hscs-activation-vi-peer-reviewed-article-DDDTEndostatinLiver fibrogenesisHepatic stellate cell (HSC)Signal pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ren H Li Y Chen Y Wang L |
spellingShingle |
Ren H Li Y Chen Y Wang L Endostatin attenuates PDGF-BB- or TGF-β1-induced HSCs activation via suppressing RhoA/ROCK1 signal pathways Drug Design, Development and Therapy Endostatin Liver fibrogenesis Hepatic stellate cell (HSC) Signal pathway |
author_facet |
Ren H Li Y Chen Y Wang L |
author_sort |
Ren H |
title |
Endostatin attenuates PDGF-BB- or TGF-β1-induced HSCs activation via suppressing RhoA/ROCK1 signal pathways |
title_short |
Endostatin attenuates PDGF-BB- or TGF-β1-induced HSCs activation via suppressing RhoA/ROCK1 signal pathways |
title_full |
Endostatin attenuates PDGF-BB- or TGF-β1-induced HSCs activation via suppressing RhoA/ROCK1 signal pathways |
title_fullStr |
Endostatin attenuates PDGF-BB- or TGF-β1-induced HSCs activation via suppressing RhoA/ROCK1 signal pathways |
title_full_unstemmed |
Endostatin attenuates PDGF-BB- or TGF-β1-induced HSCs activation via suppressing RhoA/ROCK1 signal pathways |
title_sort |
endostatin attenuates pdgf-bb- or tgf-β1-induced hscs activation via suppressing rhoa/rock1 signal pathways |
publisher |
Dove Medical Press |
series |
Drug Design, Development and Therapy |
issn |
1177-8881 |
publishDate |
2019-01-01 |
description |
Haitao Ren,1 Yuan Li,2 Yan Chen,3 Liang Wang4 1Department of Burns and Wound Care Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China; 2Department of Ultrasound, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China; 3Emergency Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China; 4Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China 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 (P<0.01). The expression of collagen I and F-actin was significantly upregulated in both TGF-β1 and PDGF-BB groups than in the control group (P<0.01). Both the collagen I and F-actin expression were downregulated significantly in the endostatin-treated groups (P<0.05). Endostatin significantly inhibited the upregulated expression of α-smooth muscle actin, RhoA, and ROCK1 induced by TGF-β1 or PDGF-BB (P<0.01).Conclusion: These results suggested that endostatin inhibited TGF-β1- or PDGF-BB-induced fibrosis in HSCs by modulating RhoA/ROCK signal pathways.Keywords: endostatin, liver fibrogenesis, hepatic stellate cell, signal pathways, fibrosis |
topic |
Endostatin Liver fibrogenesis Hepatic stellate cell (HSC) Signal pathway |
url |
https://www.dovepress.com/endostatin-attenuates-pdgf-bb--or-tgf-beta1-induced-hscs-activation-vi-peer-reviewed-article-DDDT |
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