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Departments of 2 Physiology and 1 Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109; and 3 National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892
The discovery that
15-deoxy-
12,14-prostaglandin
J2
(15d-PGJ2) is a ligand for the
-isoform of peroxisome proliferator-activated receptor (PPAR)
suggests nuclear signaling by prostaglandins. Studies were undertaken
to determine the nephron localization of PPAR isoforms and their
heterodimer partners, retinoid X receptors (RXR), and to evaluate the
function of this system in the kidney. PPAR
mRNA, determined by
RT-PCR, was found predominately in cortex and further localized to
proximal convoluted tubule (PCT); PPAR was abundant in renal inner
medulla, localized to inner medullary collecting duct (IMCD) and renal
medullary interstitial cells (RMIC); PPAR
, the ubiquitous form of
PPAR, was abundant in all nephron segments examined. RXR was
localized to PCT and IMCD, whereas RXR was expressed in almost all
nephron segments examined. mRNA expression of acyl-CoA synthase (ACS),
a known PPAR target gene, was stimulated in renal cortex of rats fed
with fenofibrate, but the expression was not significantly altered in
either cortex or inner medulla of rats fed with troglitazone. In
cultured RMIC cells, both troglitazone and
15d-PGJ2 significantly inhibited cell proliferation and dramatically altered cell shape by induction of
cell process formation. We conclude that PPAR and RXR isoforms are
expressed in a nephron segment-specific manner, suggesting distinct
functions, with PPAR being involved in energy metabolism through
regulating ACS in PCT and with PPAR being involved in modulating
RMIC growth and differentiation.
15-deoxy-12,14-prostaglandin
J2; reverse
transcription-polymerase chain reaction; acyl-coenzyme A synthase; microdissected nephron segments
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