Hydroxycamptothecin induces apoptosis of fibroblasts and prevents intraarticular scar adhesion in rabbits by activating the IRE-1 signal pathway

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• 作者：Xiaolei Li^a ; ¹ ; Yu Sun^b ; ¹ ; Hui Chen^b ; Gengyao Zhu^b ; Yuan Liang^b ; Qiang Wang^b ; Jingcheng Wang^b ; ^{jingchengwyz@163.com" class="auth_mail" title="E-mail the corresponding author} ; Lianqi Yan^b ; ^{yanlianqi@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Fibroblast apoptosis ; IRE-1 signal pathway ; Hydroxycamptothecin ; Intraarticular scar adhesion
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：781
• 期：Complete
• 页码：139-147
• 全文大小：2387 K

文摘

Hydroxycamptothecin (HCPT) has been proven to prevent intraarticular scar adhesion, but the mechanism is still unclear. ER stress is known to participate in many diseases, and the IRE-1 signal pathway has been reported in fibrotic diseases. The aim of this study was to illustrate the mechanism of HCPT-induced apoptosis in fibroblasts and the prevention of intraarticular scar adhesion. The effects of HCPT on fibroblasts were determined by CCK-8 assay, Hoechst staining and Western blot. The effect of HCPT on intraarticular scar adhesion was detected by macroscopic evaluation, hydroxyproline content, histological evaluation, fibroblast counting and immunohistochemical analysis. HCPT induced apoptosis of fibroblasts, according to CCK-8 assays, Hoechst staining and Western blot analysis. As the concentration of HCPT increased, the expressions of glucose-regulated protein 78 (GRP78), inositol-requiring kinase1 (IRE-1), C/EBP homologous protein (CHOP) and Bax were all increased, but the expression of Bcl-2 was decreased. Knockdown of IRE-1 alleviated the HCPT-induced apoptosis in our fibroblast model. HCPT could prevent intraarticular scar adhesion, according to the results of macroscopic evaluation, hydroxyproline content, histological evaluation and fibroblast counting in a rabbit model. Immunohistochemical analysis showed that IRE-1 expression increased as the concentration increased. The present study showed that the IRE-1 signal pathway might be involved in HCPT-induced apoptosis of fibroblast and might play a role in preventing intraarticular scar adhesion.