Differential mrna expression of the insulin-like growth factor
system during renal injury and hypertrophy.
Hise, Michael K., Liu Li, Nicki Mantzouris, and Richard M. Rohan.
Division of Nephrology, Department of Internal Medicine, University
of Maryland Medical School, Division of Reproductive Endocrinology,
Department of Obstetrics and Gynecology, University of Maryland
Medical School
APStracts 2:0099F, 1995.
The cellular effects of IGF-I are modified by a family of binding
proteins (IGFBPs) which act as reservoirs in serum for the growth
factor and are produced locally by tissues including the kidney.
Since regulation of these proteins may influence renal repair either
directly or by their interactions with IGF-I, we studied gene
expression during the recovery from renal failure induced by folic
acid (FA) and during the compensatory increase in renal function
following uninephrectomy (UNx). Expression of IGF-I, the IGF-I
receptor (IGF-IR) and all six IGFBPs were detected using an RNase
protection assay. IGFBP-5 was the most abundant binding protein mRNA
present in kidney while IGFBP-2 and 6 were the least abundant. During
regeneration following folic acid induced acute renal failure, IGF-I,
IGFBP-3, and IGFBP-5 mRNAs declined in abundance 2-3 fold. On the
other hand, IGF-IR, IGFBP-1, and IGFBP-2 were increased (2-, 6-, and
6-fold respectively) in the first 24 hours. IGFBP-1 mRNA remained
elevated for at least 3 days. Despite the known increase in cellular
RNA content following UNx, little difference in specific expression
of mRNAs were observed. Since IGFBP-1 has been shown to stimulate
cell migration and has previously been localized to the distal
nephron, the site of greatest injury in the folic acid model, these
data are compatible with the notion that this protein may function
either directly to affect cellular repair or act as a reservoir for
IGF-I under conditions of cellular damage.
Received 11 April 1995; accepted in final form 6 June 1995.
APS Manuscript Number F122-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.