Time-dependent alterations of select genes in streptozotocin-induced diabetic rat bladder.
OBJECTIVE
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.
Gray
Margaret A
MA
Department of Bioengineering, Clemson University, Clemson, South Carolina 29634-0905, USA.
Wang
Chung-Cheng
CC
Sacks
Michael S
MS
Yoshimura
Naoki
N
Chancellor
Michael B
MB
Nagatomi
Jiro
J
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D001743:Urinary Bladder / Q000378:metabolism
D016326:Extracellular Matrix Proteins