Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder
AuthorsHindi, Emad A.
Williams, Craig J.
Zeef, Leo A. H.
Lopes, Filipa M.
Davey, Martha M. M.
Hodson, Nigel W.
Hilton, Emma N.
Huang, Jennifer L.
Price, Karen L.
Roberts, Neil A.
Long, David A.
Woolf, Adrian S.
Gardiner, Natalie J.; email: firstname.lastname@example.org
MetadataShow full item record
AbstractAbstract: 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.
CitationScientific Reports, volume 11, issue 1, page 15529
PublisherNature Publishing Group UK
DescriptionFrom Springer Nature via Jisc Publications Router
History: received 2020-09-28, accepted 2021-06-30, registration 2021-07-13, pub-electronic 2021-07-30, online 2021-07-30, collection 2021-12
Publication status: Published
Funder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/L002744/1, MR/T016809/1, MR/L002744/1, MR/L002744/1
Funder: Diabetes UK; doi: http://dx.doi.org/10.13039/501100000361; Grant(s): 15/0005283, 15/0005283