Full Text:   <624>

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CLC number: R34

On-line Access: 2017-11-06

Received: 2017-01-25

Revision Accepted: 2017-05-07

Crosschecked: 2017-10-20

Cited: 0

Clicked: 1817

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Hai-tao Ren

http://orcid.org/0000-0003-2588-9523

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Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.11 P.994-1001

http://doi.org/10.1631/jzus.B1700052


Endostatin inhibits fibrosis by modulating the PDGFR/ERK signal pathway: an in vitro study


Author(s):  Yuan Li, Hai-tao Ren

Affiliation(s):  Department of Ultrasound, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China; more

Corresponding email(s):   docliyuan@zju.edu.cn, rht@zju.edu.cn

Key Words:  Endostatin, Hypertrophic scar, Phosphorylated platelet-derived growth factor receptor (p-PDGFR), Extracellular signal-regulated kinase (ERK), Signal pathway


Yuan Li, Hai-tao Ren. Endostatin inhibits fibrosis by modulating the PDGFR/ERK signal pathway: an in vitro study[J]. Journal of Zhejiang University Science B, 2017, 18(11): 994-1001.

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Abstract: 
Accumulating evidence indicates that endostatin inhibits fibrosis. However, the mechanism is yet to be clarified. The aim of this study is to evaluate the effect of endostatin on platelet-derived growth factor-BB (PDGF-BB)- or transforming growth factor β1 (TGF-β1)-induced fibrosis in cultured human skin fibroblasts, and to further examine the molecular mechanisms involved. Human dermal fibroblasts were cultured in Dulbecco’s modified Eagle’s medium (DMEM) and serum-starved for 48 h before treatment. Cells were grouped as follows: “PDGF-BB”, “PDGF-BB+ endostatin”, “TGF-β1”, “TGF-β1+endostatin”, “endostatin”, and “blank control”. The fibroblasts were stimulated with either TGF-β1 or PDGF-BB for 72 h in order to set up the fibrosis model in vitro. The cells were co-cultured with either TGF-β1 or PDGF-BB and endostatin and were used to check the inhibiting effect of endostatin. A blank control group and an endostatin group were used as negative control groups. The biomarkers of fibrosis, including the expression of collagen I, hydroxyproline, and α-smooth muscle actin (α-SMA), were evaluated using an enzyme-linked immunosorbent assay (ELISA) and Western blot. The expression of phosphorylated PDGF receptor β (p-PDGFRβ), PDGFRβ, phosphorylated extracellular signal-regulated kinase (p-ERK), and ERK was detected using Western blot and immunofluorescent staining was used to explore the mechanisms. Both PDGF-BB and TGF-β1 significantly up-regulated the expression of collagen I, hydroxyproline, and α-SMA. endostatin significantly attenuated both the PDGF-BB- and TGF-β1-induced over-expression of collagen I, hydroxyproline, and α-SMA. PDGF-BB and TGF-β1 both promoted the expression of PDGFR, ERK, and p-ERK. endostatin inhibited the expression of PDGFR and p-ERK but did not affect the expression of total ERK. endostatin inhibited hypertrophic scar by modulating the PDGFRβ/ERK pathway. endostatin could be a promising multi-target drug in future fibrosis therapy.

内皮抑素通过调控PDGFR/ERK信号通路抑制人成纤维细胞纤维化的研究

目的:近年来发现内皮抑素可以抑制组织纤维化,但是具体机制不详。本文旨在研究内皮抑素抑制纤维化的作用机制。
创新点:首次阐明了内皮抑素对成纤维细胞PDGFRβ(血小板衍生生长因子受体β)/ERK(细胞外调节蛋白激酶)信号通路的影响及其与纤维化的关系。
方法:体外培养人成纤维细胞,采用血小板衍生生长因子-BB(PDGF-BB)或转化生长因子-β1(TGF-β1)建立细胞纤维化模型,进一步应用内皮抑素处理,通过检测胶原及肌成纤维细胞表面标志等了解内皮抑素对细胞纤维化和表型转化的抑制作用。进而检测内皮抑素对成纤维细胞PDGFRβ/ERK信号通路的影响,并分析其可能与抗纤维化作用存在的关联。
结论:内皮抑素通过调控PDGFRβ/ERK信号通路抑制瘢痕增生,是多靶点的、具有较好的抗纤维化临床应用前景的药物。

关键词:内皮抑素;增生性瘢痕;血小板衍生生长因子受体;细胞外信号调节激酶;信号通路

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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