Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder.
Experimental long-term diabetes mellitus alters the transcriptome and biomechanical properties of the rat urinary bladder.
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实验性长期糖尿病改变大鼠膀胱的转录组和生物力学特性。
DOI：
10.1038/s41598-021-94532-7
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发表时间：
2021-07-30
影响因子：
4.6
通讯作者：
Gardiner NJ
中科院分区：
文献类型：
--
作者：
Hindi EA;Williams CJ;Zeef LAH;Lopes FM;Newman K;Davey MMM;Hodson NW;Hilton EN;Huang JL;Price KL;Roberts NA;Long DA;Woolf AS;Gardiner NJ
糖尿病（DM）是慢性肾脏疾病的主要病因，糖尿病肾病被广泛研究。相比之下，尽管排尿功能障碍在糖尿病中很常见，但糖尿病膀胱疾病的病理生物学尚不清楚。我们假设糖尿病膀胱病变具有特征性的分子特征。因此，我们研究了链脲霉素（STZ）诱导DM的高血糖和多尿大鼠的膀胱。诱导DM后16周，通过RNA阵列评估，糖尿病膀胱中基因表达的广泛变化超过了非高血糖糖诱导的多尿大鼠膀胱中基因表达的变化。改变的转录本包括细胞外基质调节因子和神经分子的编码。在db/db小鼠膀胱中也检测到DM大鼠膀胱中关键基因失调控的变化。在DM大鼠膀胱中，逼尿肌束之间的双折射胶原减少，原子力显微镜显示组织硬度明显降低；蔗糖处理大鼠的膀胱没有发现这两种变化。因此，细胞外基质的改变和组织硬度的降低可能会导致长期糖尿病患者的排尿功能障碍。这些结果为理解糖尿病性膀胱病变的复杂病理生物学奠定了基础。
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.
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影响因子：
6.6
作者：
Daneshgari, Firouz;Liu, Guiming;Imrey, Peter B.
通讯作者：
Imrey, Peter B.
DOI：
10.1152/ajprenal.00021.2020
发表时间：
2020-04-01
影响因子：
4.2
作者：
Hodrea, Judit;Balogh, Dora B.;Fekete, Andrea
通讯作者：
Fekete, Andrea
影响因子：
1.6
作者：
Inaba, Mitsuhiko;Ukimura, Osamu;Miki, Tsuneharu
通讯作者：
Miki, Tsuneharu
影响因子：
3.5
作者：
Cheng F;Birder LA;Kullmann FA;Hornsby J;Watton PN;Watkins S;Thompson M;Robertson AM
通讯作者：
Robertson AM
DOI：
10.1016/j.juro.2009.08.070
发表时间：
2009-12
期刊：
The Journal of urology
影响因子：
--
作者：
Daneshgari F;Liu G;Birder L;Hanna-Mitchell AT;Chacko S
通讯作者：
Chacko S