Puberty permits increased expression of renal transforming growth factor-beta1 in experimental diabetes.
Prepubertal years of diabetes mellitus are relatively protected from clinical manifestations of nephropathy. Transforming growth factor-beta1 (TGF-beta1) is a major mediator of diabetic kidney disease. Its renal expression, translation, and activation change with sexual maturation in the normal rat. The role of TGF-beta1 in postpubertal susceptibility to diabetic renal hypertrophy was addressed in the present study. Male Sprague- Dawley rats were given streptozocin at 4 weeks of age (weanling) or 14 weeks of age (mature) and treated with insulin to maintain blood glucose levels between 300 and 500 mg/dl. Nondiabetic controls received saline. After 6 weeks with ad libitum food and water, kidneys were snap-frozen for measurement of TGF-beta1 protein and mRNA. As in previous studies, diabetic renal hypertrophy was blunted in weanling animals compared with mature rats. Message for TGF-beta1 was not significantly increased in weanling animals [102 (9)% [mean (SEM)] in nondiabetic controls versus 117 (10)% in diabetic rats; P=0.91], while it was significantly increased in mature diabetic animals [100 (7)% vs. 146 (11)%; P=0.01]. Immunohistochemistry revealed focal increases in glomerular staining in mature but not weanling diabetic rats. Differences in the control of the renal TGF-beta system may explain the permissive role of puberty in the manifestations of diabetic kidney disease.
Lane
P H
PH
Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198-2169, USA. Phlane@unmc.edu
Snelling
D M
DM
Hollman
A
A
Langer
W J
WJ
D000375:Aging / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1