Cell-specific regulation of mRNAs for IGF-I and IGF-binding proteins-4 and -5 in streptozotocin-diabetic rat kidney.
Streptozotocin (STZ)-induced diabetes in the rat causes early renal enlargement preceded by a transient elevation in IGF-I content and an increase in IGF-I tissue binding. The effects of IGF-I are mainly mediated through the IGF-I receptor (IGF-IR) and modulated by six specific IGF-binding proteins (IGFBPs). We investigated the gene expression of IGF-I, IGF-IR and IGFBPs at a cellular level within the kidney using in situ hybridisation techniques in short-term (7 day) STZ-diabetic, insulin-treated euglycaemic and normal rats. In diabetes, IGFBP-1 mRNA showed markedly increased expression in distal tubules, collecting ducts and thick ascending limbs of Henle (TALs). IGF-I, and IGFBP-4 and -5 mRNAs showed site-specific tubular changes whilst remaining unchanged in other parts of the kidney normally expressing the genes: IGF-I and IGFBP-4 mRNAs were reduced in TALs and proximal tubules respectively; IGFBP-5 mRNA was reduced in most distal tubular cells but strongly expressed in a few of these cells. IGF-IR mRNA and the mRNAs for IGFBP-2, -3 and -6 were unchanged in STZ diabetes. There was no difference between control and insulin-treated kidneys. These complex changes suggest possible involvement of the IGF/IGFBP system in the early stages of diabetic renal hypertrophy.
Price
G J
GJ
Centre for Hormone Research, Royal Children's Hospital, Parkville, Victoria, Australia.
Berka
J L
JL
Werther
G A
GA
Bach
L A
LA
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D006651:Histocytochemistry; D017403:In Situ Hybridization; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I