title: Endoplasmic reticulum stress is involved in apoptosis of detrusor muscle in streptozocin-induced diabetic rats.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: First College of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, China.|Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Dongwen
authors.initials: D
authors.lastname: Wang
authors.affiliation: First College of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, China.|Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Yuan
authors.affiliation: First College of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, China.|Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Caoyang
authors.initials: C
authors.lastname: Hu
authors.affiliation: First College of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, China.|Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: First College of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, China.|Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Gao
authors.affiliation: First College of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, China.|Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: First College of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, China.|Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Chi
authors.affiliation: First College of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, China.|Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Jing
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Shulin
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Chin-Lee
authors.initials: CL
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D053454:Caspase 12 / Q000096:biosynthesis / Q000235:genetics; D048909:Diabetes Complications / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000473:pathology / Q000648:ultrastructure; D059865:Endoplasmic Reticulum Stress; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D020287:In Situ Nick-End Labeling; D009130:Muscle, Smooth / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D051742:Transcription Factor CHOP / Q000096:biosynthesis / Q000235:genetics; D001743:Urinary Bladder / Q000473:pathology* / Q000648:ultrastructure; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D015415:Biomarkers; D053454:Caspase 12; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C506443:Casp12 protein, rat
keywords: apoptosis; diabetic cystopathy; endoplasmic reticulum stress