Inhibitory effect of recombinant human endostatin on the proliferation of hypertrophic scar fibroblasts in a rabbit ear model

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• 作者：Yong-Fang Gong^a ; ^{gyfanhui@126.com" class="auth_mail" title="E-mail the corresponding author} ; Xiao-Ming Zhang^a ; ^{zhxm_1919@126.com" class="auth_mail" title="E-mail the corresponding author} ; Fei Liu^a ; ^{liufei1016@163.com" class="auth_mail" title="E-mail the corresponding author} ; Zhen-Zhen Wang^a ; ^{wangzz190@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Xue-Fei Deng^a ; ^{knowou@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yi Jiao^a ; ^{jiaoyi7721@aliyun.com" class="auth_mail" title="E-mail the corresponding author} ; Xiao-Jing Li^b ; ^{ahzyangel@sina.com" class="auth_mail" title="E-mail the corresponding author} ; Xue-Ying Huang^a ; ^{hxy8676@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Recombinant human endostatin ; Hypertrophic scar ; Fibroblast ; Proliferation
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：791
• 期：Complete
• 页码：647-654
• 全文大小：1155 K

文摘

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 100 mg/L. Also, rhEndostatin (100 mg/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.