No Evidence of Fibrosis Associated with Urinary Bladder Enlargement in Rodent Models of Type 2 Diabetes

Abstract ID 93369 Poster Board 202 Introduction Fibrosis typically occurs in hypertrophied tissue including the urinary bladder but has repeatedly been reported to be absent in bladder enlargement in the streptozotocin (STZ) induced model of type 1 diabetes (T1DM). However, no information is present on type 2 diabetes (T2DM), where enlargement occurs in many but not all models. Methods Five rodent models were studied: STZ-induced T1DM in rats as positive control; ZSF rats, rats exposed to high-fat diet (HFD) + low-dose STZ, and db/db and ob/ob mice as T2DM models. The presence of fibrosis was assessed by Masson-Goldner staining; additionally, mRNA expression of collagen I and III and of TGF-β was assessed by qPCR with double normalization for β-actin and GAPDH. Results STZ, HFD+STZ and ZSF rats exhibited marked bladder enlargement (about doubled weight) and ob/ob mice a moderate bladder enlargement, whereas db/db mice did not (negative control). None of the five models exhibited a major increase in connective tissue staining: STZ rats +16% [95% CI −9; +41], HFD/STZ rats +15% [−8; 39], db/db −9% [−21; +2] and ob/ob mice 0% [−12; +12]; connective tissue staining was reduced by 29% [95% CI −11; −47] in ZSF rats. The mRNA expression of β-actin and GAPDH was not affected in the disease groups allowing to use them as reference genes for normalization of the mRNA data. The mRNA expression of collagens I and III and of TGF-β was not increased in any of the models. For instance, the mean difference for collagen I was −19% [−87; +48] in STZ rats, +20% [−45; +84] in ZSF rats, and −14% [−38; +9] in db/db mice. If anything, it was reduced by −42% [−60; −24] in ob/ob mice. Conclusions We conclude that lack of fibrosis despite major enlargement of the urinary bladder is not limited to rodent models of T1DM but also seen in those of T2DM. These data further support that the pathophysiology of diabetes-associated bladder enlargement differs from that of non-diabetic causes of bladder hypertrophy. Funding DFG Mi 294-10/1 and TÜBITAK-SBAG 118S443.