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Autophagy Alters Bladder Angiogenesis and Improves Bladder Hyperactivity in the Pathogenesis of Ketamine-Induced Cystitis in a Rat Model

Authors :
Jian-He Lu
Yi-Hsuan Wu
Tai-Jui Juan
Hung-Yu Lin
Rong-Jyh Lin
Kuang-Shun Chueh
Yi-Chen Lee
Chao-Yuan Chang
Yung-Shun Juan
Source :
Biology, Vol 10, Iss 6, p 488 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

The present study attempts to elucidate whether autophagy alters bladder angiogenesis, decreases inflammatory response, and ameliorates bladder hyperactivity—thereby influencing bladder function in ketamine-induced cystitis (KIC). In our methodology, female Sprague-Dawley (S-D) rats were randomly divided into the control group, the ketamine group, the ketamine+rapamycin group, and the ketamine+wortmannin group. The bladder function, contractile activity of detrusor smooth muscle, distribution of autophagosome and autolysosome, total white blood cells (WBCs) and leukocyte differential counts, the expressions of autophagy-associated protein, angiogenesis markers, and signaling pathway molecules involved in KIC were tested, respectively. The data revealed that treatment with ketamine significantly results in bladder overactivity, enhanced interstitial fibrosis, impaired endothelium, induced eosinophil-mediated inflammation, swelling, and degraded mitochondria and organelles, inhibited angiogenesis, and elevated the phosphorylation of Akt. However, treatment with rapamycin caused an inhibitory effect on vascular formation, removed ketamine metabolites, decreased the eosinophil-mediated inflammation, and ameliorated bladder hyperactivity, leading to improve bladder function in KIC. Moreover, wortmannin treatment reduced basophil-mediated inflammatory response, improved bladder angiogenesis by increasing capillary density and VEGF expression, to reverse antiangiogenic effect to repair KIC. In conclusion, these findings suggested that autophagy could modulate inflammatory responses and angiogenesis, which improved bladder function in KIC.

Details

Language :
English
ISSN :
20797737
Volume :
10
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.9575d282ab38476d8c8f4413882c702b
Document Type :
article
Full Text :
https://doi.org/10.3390/biology10060488