Insulin-like growth factor I regulates renal development in rodents

Autor: Marc R. Hammerman, Lyn Powell-Braxton, Sharon A. Rogers
Rok vydání: 1999
Předmět:
Zdroj: Developmental Genetics. 24:293-298
ISSN: 1520-6408
0192-253X
DOI: 10.1002/(sici)1520-6408(1999)24:3/4<293::aid-dvg12>3.0.co;2-s
Popis: Blocking the action of insulin-like growth factor I (IGF I) impairs kidney development in vitro. However, no renal developmental abnormalities have been reported in newborn transgenic mice that do not express IGF I (Igf1−/−) mice. Ninety-five percent of Igf1−/− mice die immediately following birth. Kidney development continues following birth in rodents. To readdress the question of the participation of IGF I in the process of kidney development, we measured nephron numbers in developed kidneys from Igf1−/− mice that survived past birth, and using a second model of kidney development, characterized the effect of IGF I infused into rat hosts on the renal function of transplanted metanephroi. Igf1−/− mice were born with grossly normal kidneys. At 77 ± 10 days after birth, Igf1−/− mice that survived were approximately 28% the weight of wild-type (WT) littermates and had proportionally smaller kidneys. The number of nephrons per kidney was reduced by approximately 20% in Igf1−/− mice. Glomerular size was also reduced in Igf1−/− mice. In untreated host rats, neither the size nor inulin clearance of transplanted metanephroi changed significantly from 12–28 weeks postimplantation. The administration of IGF I to hosts did not affect the size of transplanted metanephroi measured at 12–16 weeks following implantation. However, inulin clearances were increased significantly by the administration of IGF I to hosts. Our findings 1) indicate that IGF I plays a role in determining nephron number, 2) suggest that it enhances function in developing kidneys, and 3) establish the potential for the pharmacological use of IGF I to enhance the growth and function of transplanted metanephroi. Dev. Genet. 24:293–298, 1999. © 1999 Wiley-Liss, Inc.
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