Decreased autophagic activity of detrusor cells is involved in the inflammatory response of interstitial cystitis/bladder pain syndrome

• Published in: International Urogynecology Journal 2023-04, Vol.34 (4), p.843-851
• Main Authors: Zhao, Jiang, Lu, Qudong, Yang, Zhengxin, Sun, Bishao, Zhu, Jingzheng, Zhang, Hengshuai, Yang, Chengfei, Yi, Shanghong, Dong, Xinyou
• Format: Article
• Language: English
• Subjects: Apoptosis; Autophagy; bcl-2-Associated X Protein; Bladder; Caspase 3; Cystitis, Interstitial - metabolism; Genome-Wide Association Study; Gynecology; Humans; Inflammation; Interleukin-6; Medicine; Medicine & Public Health; Original Article; Tumor Necrosis Factor-alpha; Urology
• ISSN: 0937-3462; 1433-3023
• DOI: 10.1007/s00192-022-05224-3

Introduction and hypothesis Genome-wide association studies suggest that autophagy plays an important regulatory role in inflammatory and autoimmune diseases. Inflammation and immune regulation disorders are involved in the occurrence and development of interstitial cystitis/bladder pain syndrome (IC/BPS). However, the changes and roles of autophagy in IC/BPS have not been reported. Therefore, this study aimed to investigate bladder autophagy and inflammation changes in patients with IC/BPS. Methods Bladder specimens ( n = 5) from patients with cystectomy due to end-stage IC/BPS were collected. The bladder samples of the control group ( n = 5) were derived from the normal area bladder tissue after radical cystectomy. H&E and toluidine blue staining were used for histological evaluation. The co-location of LC3, alpha-smooth muscle actin (α-SMA), and autophagosome was investigated with double-labeled immunofluorescence and transmission electron microscopy (TEM). The expression of IL-6, TNF-α, Bax, caspase-3, and BCL-2 in the detrusor layer was analyzed using immunohistochemistry (IHC) and Western blot (WB). Results Compared with the control group, bladder tissue from IC/BPS patients revealed thinner and edematous epithelium with many mast cells ( P < 0.05) infiltrating into the muscle layer. By using TEM ( P < 0.05), double-labeled immunofluorescence ( P < 0.05), and Western blot ( P < 0.05) in IC/BPS patients, autophagy was also found and was significantly increased in detrusor myocytes. IHC and WB indicate the expression of BCL-2 ( P < 0.05) was decreased, while IL-6, TNF-α, Bax, and caspase-3 expression was elevated ( P < 0.05). Conclusions The number of autophagosomes in detrusor cells was increased in IC/BPS. However, autophagy of detrusor muscle cells may not have sufficient phagocytic activity to effectively remove damaged proteins and mitochondria, which may lead to the continued deterioration of IC/BPS inflammation and apoptosis.