title: Hydroxycamptothecin induces apoptosis of fibroblasts and prevents intraarticular scar adhesion in rabbits by activating the IRE-1 signal pathway.
abstract: 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.
authors.affiliation: Department of Orthopedics, The Second Xiangya Hospital Affiliated with Central South University, Changsha 410011, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
authors.forename: Gengyao
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China. Electronic address: jingchengwyz@163.com.
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou 225001, China. Electronic address: yanlianqi@126.com.
authors.forename: Lianqi
authors.initials: L
authors.lastname: Yan
mesh_terms: D000268:Adhesiveness; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004722:Endoribonucleases / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D008297:Male; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D003094:Collagen; D004722:Endoribonucleases; D006909:Hydroxyproline; D002166:Camptothecin
keywords: Fibroblast apoptosis; Hydroxycamptothecin; IRE-1 signal pathway; Intraarticular scar adhesion