Time-Dependent Alterations of Select Genes in Streptozotocin-Induced Diabetic Rat Bladder

Abstract

Objectives: To investigate time-course changes in the expression of select genes and extracellular matrix proteins in the bladder of rats with streptozotocin-induced diabetes, so as to examine the mechanisms underlying changes in mechanical properties of the bladder due to diabetic cystopathy. Methods: Female Sprague-Dawley rats were injected with streptozotocin (65 mg/kg). Rats that were fed with 5% sucrose in drinking water served as diuretic controls, in addition to normal control rats. At the end of 2, 4, and 8 weeks, total ribonucleic acid (RNA) isolated from the detrusor layer of the bladders was reverse transcribed, and then complementary deoxyribonucleic acid was amplified with polymerase chain reaction primer sets for type I collagen, type III collagen, tropoelastin, and transforming growth factor beta 1 (TGF-beta-1). Collagen and elastin contents of the bladders were quantified with commercially available assays. Results: Both diabetic and diuretic rat bladders exhibited significantly (P <0.05) lower expression of type I collagen and TGF-beta-1 messenger RNA (mRNA) compared with normal controls at all time points tested. In contrast, downregulation of type III collagen mRNA expression in both diabetic and diuretic groups was seen at 4 and 8 weeks. Furthermore, tropoelastin mRNA expression in the diabetic rat bladders was, compared with normal and diuretic rats, significantly (P <0.05) greater at 2 weeks. Both diabetic and diuretic rat bladders exhibited significantly (P <0.05) decreased collagen and increased elastin protein content at 2 and 8 weeks. Conclusions: The results of the present study suggest that increases in compliance of the bladders in diabetic cystopathy result not only from diuresis-driven reduction of collagen synthesis but also from increased elastin synthesis. © 2008 Elsevier Inc. All rights reserved.