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Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder

Hindi, EA; Williams, CJ; Zeef, LAH; Lopes, FM; Newman, K; Davey, MMM; Hodson, NW; ... Gardiner, NJ; + view all (2021) Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder. Scientific Reports , 11 , Article 15529. 10.1038/s41598-021-94532-7. Green open access

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Abstract

Diabetes mellitus (DM) is the leading cause of chronic kidney disease and diabetic nephropathy is widely studied. In contrast, the pathobiology of diabetic urinary bladder disease is less understood despite dysfunctional voiding being common in DM. We hypothesised that diabetic cystopathy has a characteristic molecular signature. We therefore studied bladders of hyperglycaemic and polyuric rats with streptozotocin (STZ)-induced DM. Sixteen weeks after induction of DM, as assessed by RNA arrays, wide-ranging changes of gene expression occurred in DM bladders over and above those induced in bladders of non-hyperglycaemic rats with sucrose-induced polyuria. The altered transcripts included those coding for extracellular matrix regulators and neural molecules. Changes in key genes deregulated in DM rat bladders were also detected in db/db mouse bladders. In DM rat bladders there was reduced birefringent collagen between detrusor muscle bundles, and atomic force microscopy showed a significant reduction in tissue stiffness; neither change was found in bladders of sucrose-treated rats. Thus, altered extracellular matrix with reduced tissue rigidity may contribute to voiding dysfunction in people with long-term DM. These results serve as an informative stepping stone towards understanding the complex pathobiology of diabetic cystopathy.

Type: Article
Title: Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-021-94532-7
Publisher version: https://doi.org/10.1038/s41598-021-94532-7
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10132337
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