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Endoplasmic reticulum stress is involved in apoptosis of detrusor muscle in streptozocin‐induced diabetic rats
Author(s) -
Wang Dongwen,
Yuan Xiaobin,
Hu Caoyang,
Zhang Bin,
Gao Hongfei,
Wang Dong,
Chi Junjie,
Jing Qiang,
Wu Shulin,
Wu ChinLee
Publication year - 2017
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.22886
Subject(s) - endoplasmic reticulum , tunel assay , apoptosis , glucose regulated protein , western blot , streptozocin , chop , medicine , unfolded protein response , in situ nick end labeling , h&e stain , terminal deoxynucleotidyl transferase , endocrinology , pathology , staining , immunohistochemistry , diabetes mellitus , biology , microbiology and biotechnology , streptozotocin , biochemistry , gene
Aims Endoplasmic reticulum stress (ERS) has been proven to be associated with apoptosis and plays a critical role in the development of many diabetic complications. In the pathogenesis of diabetic cystopathy (DCP), the role of ERS is still unclear. Our study is aimed at the investigation of the involvement of ERS‐associated detrusor muscle apoptosis in streptozocin (STZ)‐induced diabetic rats. Methods At different timepoints (4, 8, 12, and 16 weeks after induction of type 1 diabetic rat models), hematoxylin & eosin (H&E) staining was performed to assess the histological changes of the diabetic detrusor; the sub‐cellular ultrastructure, especially the zone of endoplasmic reticulum (ER), was observed by transmission electron microscopy (TEM), and the terminal deoxynucleotidyl transferase‐mediated DNA nick‐end labeling (TUNEL) staining was used to identify the enhanced apoptosis. Moreover, the expression of three hallmarks of ERS‐associated apoptosis, including glucose‐regulated protein 78 (GRP78), CCAAT/enhancer‐binding protein homologous protein (CHOP), and caspase12, was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot. Results Light microscopic impairments of histology, including progressive loosely packed muscle bundles and increased fibrous tissue, can be seen; the ultrastructural changes featuring the swollen and fused cisternaes in ER zone and deformed nucleus were also observed in the detrusor smooth muscle (DSM). Increased apoptosis and elevated expression of GRP78, CHOP, and caspase12 at both protein and mRNA levels in a time‐dependent fashion were detected. Conclusions The occurrence of ERS‐associated apoptosis may be involved in the development of DCP and may contribute to the diabetic detrusor impairment. Neurourol. Urodynam. 36:65–72, 2017 . © 2015 Wiley Periodicals, Inc.