Increased autophagy contributes to impaired smooth muscle function in neurogenic lower urinary tract dysfunction.

Eberli, Daniel; Horst, Maya; Mortezavi, Ashkan; Andersson, Karl-Erik; Gobet, Rita; Sulser, Tullio; Simon, Hans-Uwe; Salemi, Souzan (2018). Increased autophagy contributes to impaired smooth muscle function in neurogenic lower urinary tract dysfunction. Neurourology and urodynamics, 37(8), pp. 2414-2424. Wiley-Liss 10.1002/nau.23705

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AIMS To explore whether autophagy plays a role in the remodeling of bladder smooth muscle cells (SMCs) in children with neurogenic lower urinary tract dysfunction (NLUTD), we investigated the effect of autophagy in NLUTD in the paediatric population. METHODS Bladder biopsies were taken from children with NLUTD and healthy donors as controls. Samples were labeled with the SMC markers calponin, smoothelin, and the autophagy proteins LC3, ATG5, and Beclin1. The contractile ability of bladder derived SMCs was investigated. RESULTS ATG5 gene and protein was upregulated in NLUTD muscle tissue compared to normal bladder. NLUTD muscle exhibited a punctated immunostaining pattern for LC3 in a subset of the SMCs, confirming the accumulation of autophagosomes. Pronounced elevation of ATG5 in the SMC in NLUTD tissue was associated with a downregulation of the key contractile proteins smoothelin and calponin. Pharmacological blocking of autophagy completely stopped the cells growth in normal bladder SMCs. Inhibition of autophagy in the NLUTD SMCs, with already elevated levels of ATG5, resulted in a reduction of ATG5 protein expression to the basal level found in normal controls. CONCLUSIONS Our study suggests that autophagy is an important factor affecting the remodeling of SMCs and the alteration of functionality in bladder smooth muscle tissue in the NLUTD. Since autophagy can be influenced by oral medication, this finding might lead to novel strategies preventing the deterioration of NLUTD muscle.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0733-2467

Publisher:

Wiley-Liss

Language:

English

Submitter:

Jana Berger

Date Deposited:

04 Jun 2018 09:02

Last Modified:

24 Oct 2019 20:16

Publisher DOI:

10.1002/nau.23705

PubMed ID:

29797356

Uncontrolled Keywords:

autophagy muscle contraction urinary bladder

BORIS DOI:

10.7892/boris.116898

URI:

https://boris.unibe.ch/id/eprint/116898

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