Autocrine production and tgf-[beta]-mediated effects on metabolism
and viability in renal cells.
Nowak, Grayna, and Rick G. Schnellmann.
University of Arkansas for Medical Sciences, Department of
Pharmacology and Toxicology, 4301 West Markham St., Little Rock, AR
72205-7199
APStracts 3:0104F, 1996.
Transforming growth factor-[beta]1 (TGF-[beta]1) treatment (0.2-2.0
ng/ml, 8-80 pM) of confluent primary cultures of rabbit renal
proximal tubular cells (RPTC) for 6 consecutive days resulted in both
a phenotypic transformation of the monolayer into solid clusters of
cells and apoptosis. TGF-[beta]1 treatment stimulated glycolysis
before any effect on monolayer DNA content or morphology. TGF-[beta]1
treatment also resulted in a 35% decrease in oxygen consumption, 50%
inhibition of Na+/K+-ATPase activity, and a 57% decrease in
gluconeogenesis. A concentration of 0.06 ng/ml TGF-[beta]1 decreased
oxygen consumption and induced glycolysis but had no effect on
morphology and viability of RPTC. Endogenous production of TGF
-[beta]1 by RPTC increased 2.6-fold during 10 days of culture. Control
RPTC treated with anti-TGF-[beta] antibodies exhibited decreased
glycolysis, and lactate metabolism shifted from net production to net
consumption. These results show that TGF-[beta]1 stimulates
glycolysis, decreases respiration and, at higher concentrations,
induces RPTC apoptosis and phenotypic changes. Inhibition of net
lactate production in cells grown in the presence of anti-TGF-[beta]
antibodies suggests that increased endogenous production of TGF
-[beta] is responsible for the stimulation of glycolysis in long-term
cultures of RPTC.
Received 12 October 1995; accepted in final form 30 May 1996.
APS Manuscript Number F346-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96