Related Experiment Video
Updated: Feb 19, 2026
A Human Corneal Organ Culture Model of Descemet's Stripping Only with Accelerated Healing Stimulated by Engineered Fibroblast Growth Factor 1
Published on: July 22, 2022
Endostatin inhibits fibrosis by modulating the PDGFR/ERK signal pathway: an in vitro study
1Department of Ultrasound, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
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.
Insights
Endostatin effectively inhibits fibrosis by reducing collagen and alpha-SMA levels. It works by modulating the PDGF receptor beta/ERK pathway, suggesting its potential as a multi-target drug for fibrosis therapy.
Area of Science:
- Dermatology
- Cell Biology
- Biochemistry
Background:
- Fibrosis is a pathological process characterized by excessive deposition of extracellular matrix components.
- Endostatin has shown potential in inhibiting fibrosis, but its underlying mechanisms require further elucidation.
- Platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor β1 (TGF-β1) are key mediators in fibrosis development.
Purpose of the Study:
- To investigate the inhibitory effect of endostatin on PDGF-BB- or TGF-β1-induced fibrosis in human skin fibroblasts.
- To explore the molecular mechanisms by which endostatin exerts its anti-fibrotic effects.
Main Methods:
- Human dermal fibroblasts were treated with PDGF-BB or TGF-β1, with or without endostatin.
- Fibrosis biomarkers including collagen I, hydroxyproline, and α-smooth muscle actin (α-SMA) were quantified using ELISA and Western blot.
- The PDGF receptor β (PDGFRβ)/extracellular signal-regulated kinase (ERK) signaling pathway was analyzed via Western blot and immunofluorescence staining.
Main Results:
- Both PDGF-BB and TGF-β1 significantly increased collagen I, hydroxyproline, and α-SMA expression.
- Endostatin treatment markedly reduced the elevated levels of these fibrosis biomarkers.
- Endostatin inhibited the expression of PDGFRβ and phosphorylated ERK (p-ERK), indicating modulation of the PDGFRβ/ERK pathway.
Conclusions:
- Endostatin effectively attenuates PDGF-BB- and TGF-β1-induced fibrosis in human skin fibroblasts.
- The anti-fibrotic mechanism of endostatin involves the modulation of the PDGFRβ/ERK signaling pathway.
- Endostatin presents a promising therapeutic candidate for multi-target fibrosis treatment.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:16TGF - β Signaling Pathway
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal