{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:14:41Z","timestamp":1791346481985,"version":"4.3.1"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L002744\/1"],"award-info":[{"award-number":["MR\/L002744\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T016809\/1"],"award-info":[{"award-number":["MR\/T016809\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L002744\/1"],"award-info":[{"award-number":["MR\/L002744\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L002744\/1"],"award-info":[{"award-number":["MR\/L002744\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["15\/0005283"],"award-info":[{"award-number":["15\/0005283"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["15\/0005283"],"award-info":[{"award-number":["15\/0005283"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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\n                    <jats:italic>db<\/jats:italic>\n                    \/\n                    <jats:italic>db<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-94532-7","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T06:04:43Z","timestamp":1627625083000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder"],"prefix":"10.1038","volume":"11","author":[{"given":"Emad A.","family":"Hindi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig J.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A. H.","family":"Zeef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipa M.","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha M. M.","family":"Davey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel W.","family":"Hodson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma N.","family":"Hilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian S.","family":"Woolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie J.","family":"Gardiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,30]]},"reference":[{"issue":"11","key":"94532_CR1","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/j.tem.2016.07.002","volume":"27","author":"L Gnudi","year":"2016","unstructured":"Gnudi, L., Coward, R. J. M. & Long, D. A. Diabetic nephropathy: Perspective on novel molecular mechanisms. Trends Endocrinol. Metab. 27(11), 820\u2013830 (2016).","journal-title":"Trends Endocrinol. Metab."},{"issue":"2","key":"94532_CR2","first-page":"49","volume":"25","author":"C Frimodt-Moller","year":"1978","unstructured":"Frimodt-Moller, C. Diabetic cystopathy. A review of the urodynamic and clinical features of neurogenic bladder dysfunction in diabetes mellitus. Dan Med. Bull. 25(2), 49\u201360 (1978).","journal-title":"Dan Med. Bull."},{"issue":"4","key":"94532_CR3","doi-asserted-by":"publisher","first-page":"552","DOI":"10.4103\/2230-8210.137518","volume":"18","author":"R Karoli","year":"2014","unstructured":"Karoli, R., Bhat, S., Fatima, J. & Priya, S. A study of bladder dysfunction in women with type 2 diabetes mellitus. Indian J. Endocrinol. Metab. 18(4), 552\u2013557 (2014).","journal-title":"Indian J. Endocrinol. Metab."},{"issue":"2 Pt 2","key":"94532_CR4","doi-asserted-by":"publisher","first-page":"318","DOI":"10.7326\/0003-4819-92-2-318","volume":"92","author":"C Frimodt-Moller","year":"1980","unstructured":"Frimodt-Moller, C. Diabetic cystopathy: Epidemiology and related disorders. Ann. Intern. Med. 92(2 Pt 2), 318\u2013321 (1980).","journal-title":"Ann. Intern. Med."},{"issue":"4","key":"94532_CR5","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s11884-014-0255-6","volume":"9","author":"CR Powell","year":"2014","unstructured":"Powell, C. R. Is the diabetic bladder a neurogenic bladder? Evidence from the literature. Curr. Bladder Dysfunct. Rep. 9(4), 261\u2013267 (2014).","journal-title":"Curr. Bladder Dysfunct. Rep."},{"key":"94532_CR6","doi-asserted-by":"publisher","first-page":"136","DOI":"10.3389\/fphar.2010.00136","volume":"1","author":"S Golbidi","year":"2010","unstructured":"Golbidi, S. & Laher, I. Bladder dysfunction in diabetes mellitus. Front. Pharmacol. 1, 136 (2010).","journal-title":"Front. Pharmacol."},{"issue":"5","key":"94532_CR7","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/j.urology.2011.05.017","volume":"78","author":"RT Liu","year":"2011","unstructured":"Liu, R. T. et al. Prevalence of overactive bladder and associated risk factors in 1359 patients with type 2 diabetes. Urology 78(5), 1040\u20131045 (2011).","journal-title":"Urology"},{"issue":"2","key":"94532_CR8","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1097\/00005392-199502000-00013","volume":"153","author":"SA Kaplan","year":"1995","unstructured":"Kaplan, S. A., Te, A. E. & Blaivas, J. G. Urodynamic findings in patients with diabetic cystopathy. J. Urol. 153(2), 342\u2013344 (1995).","journal-title":"J. Urol."},{"issue":"6","key":"94532_CR9","doi-asserted-by":"publisher","first-page":"R1728","DOI":"10.1152\/ajpregu.00654.2005","volume":"290","author":"F Daneshgari","year":"2006","unstructured":"Daneshgari, F. et al. Temporal differences in bladder dysfunction caused by diabetes, diuresis, and treated diabetes in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290(6), R1728-1735 (2006).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"issue":"4","key":"94532_CR10","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1111\/iju.12695","volume":"22","author":"N Xiao","year":"2015","unstructured":"Xiao, N., Huang, Y., Kavran, M., Elrashidy, R. A. & Liu, G. Short-term diabetes- and diuresis-induced alterations of the bladder are mostly reversible in rats. Int. J. Urol. 22(4), 410\u2013415 (2015).","journal-title":"Int. J. Urol."},{"issue":"2","key":"94532_CR11","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/S0022-5347(17)35001-2","volume":"151","author":"B Eika","year":"1994","unstructured":"Eika, B., Levin, R. M. & Longhurst, P. A. Comparison of urinary bladder function in rats with hereditary diabetes insipidus, streptozotocin-induced diabetes mellitus, and nondiabetic osmotic diuresis. J. Urol. 151(2), 496\u2013502 (1994).","journal-title":"J. Urol."},{"issue":"6 Suppl","key":"94532_CR12","first-page":"S18","volume":"182","author":"F Daneshgari","year":"2009","unstructured":"Daneshgari, F., Liu, G., Birder, L., Hanna-Mitchell, A. T. & Chacko, S. Diabetic bladder dysfunction: Current translational knowledge. J. Urol. 182(6 Suppl), S18-26 (2009).","journal-title":"J. Urol."},{"issue":"3","key":"94532_CR13","doi-asserted-by":"publisher","first-page":"R837","DOI":"10.1152\/ajpregu.00917.2005","volume":"291","author":"G Liu","year":"2006","unstructured":"Liu, G. & Daneshgari, F. Temporal diabetes- and diuresis-induced remodeling of the urinary bladder in the rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291(3), R837-843 (2006).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"issue":"12","key":"94532_CR14","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1111\/j.1464-410X.2010.09840.x","volume":"107","author":"G Liu","year":"2011","unstructured":"Liu, G., Li, M., Vasanji, A. & Daneshgari, F. Temporal diabetes and diuresis-induced alteration of nerves and vasculature of the urinary bladder in the rat. BJU Int. 107(12), 1988\u20131993 (2011).","journal-title":"BJU Int."},{"issue":"1","key":"94532_CR15","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/S0022-5347(06)00582-9","volume":"176","author":"F Daneshgari","year":"2006","unstructured":"Daneshgari, F., Liu, G. & Imrey, P. B. Time dependent changes in diabetic cystopathy in rats include compensated and decompensated bladder function. J. Urol. 176(1), 380\u2013386 (2006).","journal-title":"J. Urol."},{"issue":"2","key":"94532_CR16","doi-asserted-by":"publisher","first-page":"E471","DOI":"10.1152\/ajpendo.00134.2016","volume":"311","author":"Y Wang","year":"2016","unstructured":"Wang, Y., Deng, G. G. & Davies, K. P. Novel insights into development of diabetic bladder disorder provided by metabolomic analysis of the rat nondiabetic and diabetic detrusor and urothelial layer. Am. J. Physiol. Endocrinol. Metab. 311(2), E471-479 (2016).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"issue":"2","key":"94532_CR17","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1111\/j.1464-410X.2007.06676.x","volume":"99","author":"JD Hipp","year":"2007","unstructured":"Hipp, J. D. et al. Using gene chips to identify organ-specific, smooth muscle responses to experimental diabetes: Potential applications to urological diseases. BJU Int. 99(2), 418\u2013430 (2007).","journal-title":"BJU Int."},{"issue":"10","key":"94532_CR18","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1111\/j.1464-410X.2010.09655.x","volume":"107","author":"ND Kanika","year":"2011","unstructured":"Kanika, N. D. et al. Oxidative stress status accompanying diabetic bladder cystopathy results in the activation of protein degradation pathways. BJU Int. 107(10), 1676\u20131684 (2011).","journal-title":"BJU Int."},{"issue":"7","key":"94532_CR19","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1074\/mcp.M700563-MCP200","volume":"7","author":"E Yohannes","year":"2008","unstructured":"Yohannes, E., Chang, J., Christ, G. J., Davies, K. P. & Chance, M. R. Proteomics analysis identifies molecular targets related to diabetes mellitus-associated bladder dysfunction. Mol. Cell. Proteom.: MCP 7(7), 1270\u20131285 (2008).","journal-title":"Mol. Cell. Proteom.: MCP"},{"key":"94532_CR20","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.molmet.2019.08.003","volume":"28","author":"S Kassab","year":"2019","unstructured":"Kassab, S. et al. Cognitive dysfunction in diabetic rats is prevented by pyridoxamine treatment. A multidisciplinary investigation. Mol. Metab. 28, 107\u2013119 (2019).","journal-title":"Mol. Metab."},{"issue":"3\u20134","key":"94532_CR21","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s10237-011-0325-z","volume":"11","author":"R Rezakhaniha","year":"2012","unstructured":"Rezakhaniha, R. et al. Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy. Biomech. Model. Mechanobiol. 11(3\u20134), 461\u2013473 (2012).","journal-title":"Biomech. Model. Mechanobiol."},{"issue":"1","key":"94532_CR22","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1073\/pnas.98.1.31","volume":"98","author":"C Li","year":"2001","unstructured":"Li, C. & Wong, W. H. Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection. Proc. Natl. Acad. Sci. U. S. A. 98(1), 31\u201336 (2001).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"2","key":"94532_CR23","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1093\/bioinformatics\/19.2.185","volume":"19","author":"BM Bolstad","year":"2003","unstructured":"Bolstad, B. M., Irizarry, R. A., Astrand, M. & Speed, T. P. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19(2), 185\u2013193 (2003).","journal-title":"Bioinformatics"},{"issue":"16","key":"94532_CR24","doi-asserted-by":"publisher","first-page":"9440","DOI":"10.1073\/pnas.1530509100","volume":"100","author":"JD Storey","year":"2003","unstructured":"Storey, J. D. & Tibshirani, R. Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. U. S. A. 100(16), 9440\u20139445 (2003).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"6","key":"94532_CR25","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1038\/ki.2013.45","volume":"83","author":"DA Long","year":"2013","unstructured":"Long, D. A. et al. Albuminuria is associated with too few glomeruli and too much testosterone. Kidney Int. 83(6), 1118\u20131129 (2013).","journal-title":"Kidney Int."},{"issue":"11","key":"94532_CR26","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/nrurol.2009.201","volume":"6","author":"KJ Aitken","year":"2009","unstructured":"Aitken, K. J. & Bagli, D. J. The bladder extracellular matrix. Part I: Architecture, development and disease. Nat. Rev. Urol. 6(11), 596\u2013611 (2009).","journal-title":"Nat. Rev. Urol."},{"key":"94532_CR27","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.matbio.2014.08.001","volume":"40","author":"C Zeltz","year":"2014","unstructured":"Zeltz, C. & Gullberg, D. Post-translational modifications of integrin ligands as pathogenic mechanisms in disease. Matrix Biol.: J. Int. Soc. Matrix Biol. 40, 5\u20139 (2014).","journal-title":"Matrix Biol.: J. Int. Soc. Matrix Biol."},{"issue":"1","key":"94532_CR28","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/S0022-5347(17)36546-1","volume":"148","author":"B Eika","year":"1992","unstructured":"Eika, B., Levin, R. M. & Longhurst, P. A. Collagen and bladder function in streptozotocin-diabetic rats: Effects of insulin and aminoguanidine. J. Urol. 148(1), 167\u2013172 (1992).","journal-title":"J. Urol."},{"issue":"4","key":"94532_CR29","doi-asserted-by":"publisher","first-page":"F1017","DOI":"10.1152\/ajprenal.00021.2020","volume":"318","author":"J Hodrea","year":"2020","unstructured":"Hodrea, J. et al. Reduced O-GlcNAcylation and tubular hypoxia contribute to the antifibrotic effect of SGLT2 inhibitor dapagliflozin in the diabetic kidney. Am. J. Physiol. Ren. Physiol. 318(4), F1017\u2013F1029 (2020).","journal-title":"Am. J. Physiol. Ren. Physiol."},{"issue":"3","key":"94532_CR30","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/j.1440-1797.2008.01059.x","volume":"14","author":"XJ Ren","year":"2009","unstructured":"Ren, X. J., Guan, G. J., Liu, G., Zhang, T. & Liu, G. H. Effect of activin A on tubulointerstitial fibrosis in diabetic nephropathy. Nephrology (Carlton) 14(3), 311\u2013320 (2009).","journal-title":"Nephrology (Carlton)"},{"issue":"2","key":"94532_CR31","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1007\/s10237-017-0968-5","volume":"17","author":"F Cheng","year":"2018","unstructured":"Cheng, F. et al. Layer-dependent role of collagen recruitment during loading of the rat bladder wall. Biomech. Model. Mechanobiol. 17(2), 403\u2013417 (2018).","journal-title":"Biomech. Model. Mechanobiol."},{"issue":"15","key":"94532_CR32","first-page":"4478","volume":"62","author":"DA Kirschmann","year":"2002","unstructured":"Kirschmann, D. A. et al. A molecular role for lysyl oxidase in breast cancer invasion. Can. Res. 62(15), 4478\u20134483 (2002).","journal-title":"Can. Res."},{"issue":"1","key":"94532_CR33","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1002\/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O","volume":"77","author":"P Beighton","year":"1998","unstructured":"Beighton, P., De Paepe, A., Steinmann, B., Tsipouras, P. & Wenstrup, R. J. Ehlers-Danlos syndromes: Revised nosology, Villefranche, 1997 Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos support group (UK). Am. J. Med. Genet. 77(1), 31\u201337 (1998).","journal-title":"Am. J. Med. Genet."},{"key":"94532_CR34","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1002\/bjs.18005021913","volume":"50","author":"GJ Clunie","year":"1962","unstructured":"Clunie, G. J. & Mason, J. M. Visceral diverticula and the Marfan syndrome. Br. J. Surg. 50, 51\u201352 (1962).","journal-title":"Br. J. Surg."},{"issue":"3","key":"94532_CR35","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/S0022-3468(99)90506-7","volume":"34","author":"JL Jorion","year":"1999","unstructured":"Jorion, J. L. & Michel, M. Spontaneous rupture of bladder diverticula in a girl with Ehlers-Danlos syndrome. J. Pediatr. Surg. 34(3), 483\u2013484 (1999).","journal-title":"J. Pediatr. Surg."},{"issue":"3","key":"94532_CR36","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1159\/000099351","volume":"78","author":"M Inaba","year":"2007","unstructured":"Inaba, M. et al. Upregulation of heme oxygenase and collagen type III in the rat bladder after partial bladder outlet obstruction. Urol. Int. 78(3), 270\u2013277 (2007).","journal-title":"Urol. Int."},{"key":"94532_CR37","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.lfs.2018.03.041","volume":"201","author":"LY Qiao","year":"2018","unstructured":"Qiao, L. Y. et al. Urinary bladder organ hypertrophy is partially regulated by Akt1-mediated protein synthesis pathway. Life Sci. 201, 63\u201371 (2018).","journal-title":"Life Sci."},{"issue":"5957","key":"94532_CR38","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1126\/science.1176009","volume":"326","author":"RO Hynes","year":"2009","unstructured":"Hynes, R. O. The extracellular matrix: Not just pretty fibrils. Science 326(5957), 1216\u20131219 (2009).","journal-title":"Science"},{"issue":"1","key":"94532_CR39","doi-asserted-by":"publisher","first-page":"a004903","DOI":"10.1101\/cshperspect.a004903","volume":"4","author":"RO Hynes","year":"2012","unstructured":"Hynes, R. O. & Naba, A. Overview of the matrisome\u2014An inventory of extracellular matrix constituents and functions. Cold Spring Harb. Perspect. Biol. 4(1), a004903 (2012).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"issue":"3","key":"94532_CR40","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1002\/art.22427","volume":"56","author":"S Sahebjam","year":"2007","unstructured":"Sahebjam, S., Khokha, R. & Mort, J. S. Increased collagen and aggrecan degradation with age in the joints of Timp3(-\/-) mice. Arthr. Rheum. 56(3), 905\u2013909 (2007).","journal-title":"Arthr. Rheum."},{"issue":"6","key":"94532_CR41","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1172\/JCI200112067","volume":"108","author":"KJ Leco","year":"2001","unstructured":"Leco, K. J. et al. Spontaneous air space enlargement in the lungs of mice lacking tissue inhibitor of metalloproteinases-3 (TIMP-3). J. Clin. Invest. 108(6), 817\u2013829 (2001).","journal-title":"J. Clin. Invest."},{"issue":"6","key":"94532_CR42","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1681\/ASN.2008050492","volume":"20","author":"Z Kassiri","year":"2009","unstructured":"Kassiri, Z. et al. Loss of TIMP3 enhances interstitial nephritis and fibrosis. J. Am. Soc. Nephrol. 20(6), 1223\u20131235 (2009).","journal-title":"J. Am. Soc. Nephrol."},{"issue":"43","key":"94532_CR43","doi-asserted-by":"publisher","first-page":"29893","DOI":"10.1074\/jbc.M109.028449","volume":"284","author":"Z Kassiri","year":"2009","unstructured":"Kassiri, Z. et al. Simultaneous transforming growth factor beta-tumor necrosis factor activation and cross-talk cause aberrant remodeling response and myocardial fibrosis in Timp3-deficient heart. J. Biol. Chem. 284(43), 29893\u201329904 (2009).","journal-title":"J. Biol. Chem."},{"issue":"3","key":"94532_CR44","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1111\/cas.13134","volume":"108","author":"Z Li","year":"2017","unstructured":"Li, Z., Takino, T., Endo, Y. & Sato, H. Activation of MMP-9 by membrane type-1 MMP\/MMP-2 axis stimulates tumor metastasis. Cancer Sci. 108(3), 347\u2013353 (2017).","journal-title":"Cancer Sci."},{"issue":"5","key":"94532_CR45","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1016\/S0022-5347(05)68995-1","volume":"161","author":"KM Azadzoi","year":"1999","unstructured":"Azadzoi, K. M., Tarcan, T., Siroky, M. B. & Krane, R. J. Atherosclerosis-induced chronic ischemia causes bladder fibrosis and non-compliance in the rabbit. J. Urol. 161(5), 1626\u20131635 (1999).","journal-title":"J. Urol."},{"issue":"5","key":"94532_CR46","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1016\/j.juro.2013.10.097","volume":"191","author":"M Nomiya","year":"2014","unstructured":"Nomiya, M. et al. Progressive vascular damage may lead to bladder underactivity in rats. J. Urol. 191(5), 1462\u20131469 (2014).","journal-title":"J. Urol."},{"issue":"1","key":"94532_CR47","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1002\/nau.23320","volume":"37","author":"B Lee","year":"2018","unstructured":"Lee, B. et al. Relationship between lower urinary tract symptoms and cardiovascular risk scores including Framingham risk score and ACC\/AHA risk score. Neurourol. Urodyn. 37(1), 426\u2013433 (2018).","journal-title":"Neurourol. Urodyn."},{"issue":"1","key":"94532_CR48","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s11255-020-02616-6","volume":"53","author":"TF Monaghan","year":"2021","unstructured":"Monaghan, T. F. et al. Cardiovascular risk independently predicts small functional bladder storage capacity. Int. Urol. Nephrol. 53(1), 35\u201339 (2021).","journal-title":"Int. Urol. Nephrol."},{"key":"94532_CR49","doi-asserted-by":"publisher","first-page":"110426","DOI":"10.1016\/j.biopha.2020.110426","volume":"129","author":"Y Zhao","year":"2020","unstructured":"Zhao, Y. et al. Small rodent models of atherosclerosis. Biomed. Pharmacother. 129, 110426 (2020).","journal-title":"Biomed. Pharmacother."},{"issue":"1","key":"94532_CR50","first-page":"327","volume":"5","author":"WC de Groat","year":"2015","unstructured":"de Groat, W. C., Griffiths, D. & Yoshimura, N. Neural control of the lower urinary tract. Compr. Physiol. 5(1), 327\u2013396 (2015).","journal-title":"Compr. Physiol."},{"issue":"2","key":"94532_CR51","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1111\/j.1464-410X.2012.11300.x","volume":"111","author":"JS Young","year":"2013","unstructured":"Young, J. S. et al. The passive and active contractile properties of the neurogenic, underactive bladder. BJU Int. 111(2), 355\u2013361 (2013).","journal-title":"BJU Int."},{"issue":"5","key":"94532_CR52","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.2337\/diacare.26.5.1553","volume":"26","author":"AI Vinik","year":"2003","unstructured":"Vinik, A. I., Maser, R. E., Mitchell, B. D. & Freeman, R. Diabetic autonomic neuropathy. Diabetes Care 26(5), 1553\u20131579 (2003).","journal-title":"Diabetes Care"},{"issue":"6","key":"94532_CR53","first-page":"1365","volume":"136","author":"S Yagihashi","year":"1990","unstructured":"Yagihashi, S., Kamijo, M. & Watanabe, K. Reduced myelinated fiber size correlates with loss of axonal neurofilaments in peripheral nerve of chronically streptozotocin diabetic rats. Am. J. Pathol. 136(6), 1365\u20131373 (1990).","journal-title":"Am. J. Pathol."},{"issue":"3","key":"94532_CR54","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1046\/j.1471-4159.1995.64031231.x","volume":"64","author":"P Fernyhough","year":"1995","unstructured":"Fernyhough, P., Diemel, L. T., Brewster, W. J. & Tomlinson, D. R. Altered neurotrophin mRNA levels in peripheral nerve and skeletal muscle of experimentally diabetic rats. J. Neurochem. 64(3), 1231\u20131237 (1995).","journal-title":"J. Neurochem."},{"issue":"3","key":"94532_CR55","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1016\/S0022-5347(05)64636-8","volume":"168","author":"K Sasaki","year":"2002","unstructured":"Sasaki, K. et al. Diabetic cystopathy correlates with a long-term decrease in nerve growth factor levels in the bladder and lumbosacral dorsal root Ganglia. J. Urol. 168(3), 1259\u20131264 (2002).","journal-title":"J. Urol."},{"issue":"10","key":"94532_CR56","doi-asserted-by":"publisher","first-page":"2723","DOI":"10.2337\/diabetes.53.10.2723","volume":"53","author":"K Sasaki","year":"2004","unstructured":"Sasaki, K. et al. Gene therapy using replication-defective herpes simplex virus vectors expressing nerve growth factor in a rat model of diabetic cystopathy. Diabetes 53(10), 2723\u20132730 (2004).","journal-title":"Diabetes"},{"issue":"3","key":"94532_CR57","doi-asserted-by":"publisher","first-page":"e91609","DOI":"10.1371\/journal.pone.0091609","volume":"9","author":"YH Jiang","year":"2014","unstructured":"Jiang, Y. H., Liu, H. T. & Kuo, H. C. Decrease of urinary nerve growth factor but not brain-derived neurotrophic factor in patients with interstitial cystitis\/bladder pain syndrome treated with hyaluronic acid. PLoS ONE 9(3), e91609 (2014).","journal-title":"PLoS ONE"},{"issue":"2","key":"94532_CR58","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s11255-013-0540-x","volume":"46","author":"LW Wang","year":"2014","unstructured":"Wang, L. W., Han, X. M., Chen, C. H., Ma, Y. & Hai, B. Urinary brain-derived neurotrophic factor: A potential biomarker for objective diagnosis of overactive bladder. Int. Urol. Nephrol. 46(2), 341\u2013347 (2014).","journal-title":"Int. Urol. Nephrol."},{"issue":"7","key":"94532_CR59","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1097\/00001756-199805110-00038","volume":"9","author":"D Oddiah","year":"1998","unstructured":"Oddiah, D., Anand, P., McMahon, S. B. & Rattray, M. Rapid increase of NGF, BDNF and NT-3 mRNAs in inflamed bladder. NeuroReport 9(7), 1455\u20131458 (1998).","journal-title":"NeuroReport"},{"issue":"1","key":"94532_CR60","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1006\/exnr.1999.7254","volume":"161","author":"MA Vizzard","year":"2000","unstructured":"Vizzard, M. A. Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction. Exp. Neurol. 161(1), 273\u2013284 (2000).","journal-title":"Exp. Neurol."},{"issue":"1","key":"94532_CR61","doi-asserted-by":"publisher","first-page":"F45","DOI":"10.1152\/ajprenal.00386.2017","volume":"315","author":"MP Kashyap","year":"2018","unstructured":"Kashyap, M. P. et al. BDNF overexpression in the bladder induces neuronal changes to mediate bladder overactivity. Am. J. Physiol. Ren. Physiol. 315(1), F45\u2013F56 (2018).","journal-title":"Am. J. Physiol. Ren. Physiol."},{"issue":"11","key":"94532_CR62","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1681\/ASN.2019040335","volume":"30","author":"Z Yu","year":"2019","unstructured":"Yu, Z. et al. Single-cell transcriptomic map of the human and mouse bladders. J. Am. Soc. Nephrol. 30(11), 2159\u20132176 (2019).","journal-title":"J. Am. Soc. Nephrol."},{"issue":"5","key":"94532_CR63","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1074\/mcp.RA117.000290","volume":"17","author":"EC Park","year":"2018","unstructured":"Park, E. C. et al. Proteomic analysis of urothelium of rats with detrusor overactivity induced by bladder outlet obstruction. Mol. Cell. Proteom. MCP 17(5), 948\u2013960 (2018).","journal-title":"Mol. Cell. Proteom. MCP"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94532-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94532-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94532-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T06:50:34Z","timestamp":1670050234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94532-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,30]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["94532"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-94532-7","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.740563950.793590459","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,30]]},"assertion":[{"value":"28 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2021","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this Article was revised: In the original version of this Article a Supplementary Figure 7 file was omitted. The Supplementary Information file now accompanies the original Article.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15529"}}