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

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 h...

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Autores principales:	Emad A. Hindi, Craig J. Williams, Leo A. H. Zeef, Filipa M. Lopes, Katie Newman, Martha M. M. Davey, Nigel W. Hodson, Emma N. Hilton, Jennifer L. Huang, Karen L. Price, Neil A. Roberts, David A. Long, Adrian S. Woolf, Natalie J. Gardiner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d05190d673047aca307800a35df1323
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spelling	oai:doaj.org-article:3d05190d673047aca307800a35df13232021-12-02T18:47:03ZExperimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder10.1038/s41598-021-94532-72045-2322https://doaj.org/article/3d05190d673047aca307800a35df13232021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94532-7https://doaj.org/toc/2045-2322Abstract 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.Emad A. HindiCraig J. WilliamsLeo A. H. ZeefFilipa M. LopesKatie NewmanMartha M. M. DaveyNigel W. HodsonEmma N. HiltonJennifer L. HuangKaren L. PriceNeil A. RobertsDavid A. LongAdrian S. WoolfNatalie J. GardinerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emad A. Hindi Craig J. Williams Leo A. H. Zeef Filipa M. Lopes Katie Newman Martha M. M. Davey Nigel W. Hodson Emma N. Hilton Jennifer L. Huang Karen L. Price Neil A. Roberts David A. Long Adrian S. Woolf Natalie J. Gardiner Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder
description	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.
format	article
author	Emad A. Hindi Craig J. Williams Leo A. H. Zeef Filipa M. Lopes Katie Newman Martha M. M. Davey Nigel W. Hodson Emma N. Hilton Jennifer L. Huang Karen L. Price Neil A. Roberts David A. Long Adrian S. Woolf Natalie J. Gardiner
author_facet	Emad A. Hindi Craig J. Williams Leo A. H. Zeef Filipa M. Lopes Katie Newman Martha M. M. Davey Nigel W. Hodson Emma N. Hilton Jennifer L. Huang Karen L. Price Neil A. Roberts David A. Long Adrian S. Woolf Natalie J. Gardiner
author_sort	Emad A. Hindi
title	Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder
title_short	Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder
title_full	Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder
title_fullStr	Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder
title_full_unstemmed	Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder
title_sort	experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3d05190d673047aca307800a35df1323
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Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder

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