Endoplasmic reticulum stress contributes to the pathogenesis of stress urinary incontinence in postmenopausal women

J Int Med Res. 2018 Dec;46(12):5269-5277. doi: 10.1177/0300060518807602. Epub 2018 Nov 14.

Abstract

Objective: To investigate the relationship between endoplasmic reticulum stress (ERS) and the pathogenesis of stress urinary incontinence (SUI) in postmenopausal women.

Methods: Anterior vaginal wall tissue was collected from postmenopausal women with SUI and control subjects. Western blotting was performed for glucose-regulated protein (GRP78), inositol-requiring enzyme 1(IRE1), protein kinase-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), C/EBP-homologous protein (CHOP), and B-cell lymphoma 2 (Bcl-2). Additionally, mRNA expression levels of PERK, activating transcription factor 4 (ATF4), and CHOP were examined by real-time polymerase chain reaction.

Results: GRP78 protein and mRNA expression levels were significantly lower in women with SUI, compared with control subjects. PERK and p-PERK expression levels were higher in women with SUI than in control subjects. However, no differences in IRE1 or ATF6 expression levels were observed in either group. Notably, higher CHOP and lower Bcl-2 protein expression levels were detected in women with SUI, compared with control subjects. Furthermore, PERK, ATF4, and CHOP mRNA expression levels were significantly higher in women with SUI than in control subjects.

Conclusions: Alterations of ERS markers in SUI suggest that ERS may be involved in the development of SUI in postmenopausal women.

Keywords: B-cell lymphoma 2; C/EBP-homologous protein; Stress urinary incontinence; activating transcription factor 4; anterior vaginal wall; apoptosis; endoplasmic reticulum stress; glucose-regulated protein; postmenopausal; protein kinase-like endoplasmic reticulum kinase.

MeSH terms

  • Activating Transcription Factor 4 / genetics
  • Activating Transcription Factor 4 / metabolism
  • Apoptosis*
  • Case-Control Studies
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress*
  • Female
  • Gene Expression Regulation*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Middle Aged
  • Postmenopause*
  • Signal Transduction
  • Transcription Factor CHOP / genetics
  • Transcription Factor CHOP / metabolism
  • Urinary Incontinence / etiology*
  • Urinary Incontinence / metabolism
  • Urinary Incontinence / pathology*
  • eIF-2 Kinase / genetics
  • eIF-2 Kinase / metabolism

Substances

  • ATF4 protein, human
  • DDIT3 protein, human
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Activating Transcription Factor 4
  • Transcription Factor CHOP
  • EIF2AK3 protein, human
  • eIF-2 Kinase