Chop Deficiency Exacerbates Cyclophosphamide-Induced Overactive Bladder via Impaired Macrophage Apoptosis.

OBJECTIVE

Overactive bladder, a storage syndrome characterized by urinary urgency, frequency, and nocturia with or without urgency urinary incontinence, severely affects the quality of life of patients. The aim of this study was to investigate the role and mechanism of the C/EBP homologous protein in the overactive bladder.

METHODS

An overactive bladder mouse model was established via the intraperitoneal injection of cyclophosphamide in wild-type and Chop-deficient mice. An in vitro model was established using interleukin (IL)-6-induced mouse bladder epithelial cells. Hematoxylin-eosin (HE) staining was used to assess bladder tissue damage, and ELISA was used to measure inflammatory cytokine levels. Western blot analysis was used to examine p-PERK, ATF-6, p-eIF2α, BiP, ATF-4, Bax, Bcl-2, and cleaved caspase-3 protein expression levels. TUNEL staining and flow cytometry were conducted to measure the degree of apoptosis in bladder epithelial cells and macrophages.

RESULTS

C/EBP homologous protein levels were decreased in overactive bladder tissues; nevertheless, macrophage infiltration was found to be increased. Knockout of Chop exacerbated bladder dysfunction, tissue injury, macrophage infiltration, and bladder epithelial apoptosis and alleviated endoplasmic reticulum stress.

CONCLUSIONS

Chop deficiency exacerbates inflammation, injury, and bladder epithelial apoptosis in overactive bladder model mice by inhibiting endoplasmic reticulum stress.