Abstract

Hypertrophic scar (HS) is a pathological scar that particularly occurs after traumatic injuries, surgical procedures and burning. Abnormal activation of hypertrophic scar fibroblasts (HSFs) intensifies fibrosis during wound healing. Our previous studies demonstrated that recombinant human endostatin (rhEndostatin) prevented synovial thickening in adjuvant arthritis (AA) rats via inhibition of proliferation and enhancement of apoptosis in synovial fibroblasts. However, the effect of this protein on HSF proliferation is not known. This study investigated the inhibitory effect of rhEndostatin on the proliferation of cultured HSFs in a rabbit ear model. MTT assay and flow cytometric detection were performed to investigate HSF proliferation and cell cycle progression, respectively. The expression levels of p53, p21, cyclinD1, cyclin-dependent kinase 4 (CDK4) and proliferating cell nuclear antigen (PCNA) in HSFs were detected using real-time PCR and Western blotting. Our data revealed that HSFs treated with rhEndostatin were significantly inhibited in a concentration-dependent manner with an IC50 value of 100mg/L. Also, rhEndostatin (100mg/L) primarily induced G0/G1 and partially G2/M cell cycle arrest of HSFs. There were significant decreases in the expression levels of p53, p27, CDK4, cyclinD1 and PCNA in HSFs treated with rhEndostatin. In conclusion, rhEndostatin inhibited HSF proliferation via G0/G1 and/or G2/M phase arrest of the cell cycle, which was partially due to the down-regulation of cyclinD1, CDK4 and PCNA. These findings suggest that rhEndostatin may reduce scar hypertrophy in vivo via inhibition of HSF proliferation and may be a novel agent for HS treatment.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.