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.