Autocrine production and TGF-beta 1-mediated effects on metabolism and viability in renal cells.
Transforming growth factor-beta 1 (TGF-beta 1) treatment (0.2-2.0 ng/ml, 8-80 M) of confluent primary cultures of rabbit renal proximal bular cells (RPTC) for 6 consecutive days resulted in both a benotypic transformation of the monolayer into solid clus- rs 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 phenopic 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.
Nowak
G
G
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
Schnellmann
R G
RG
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002455:Cell Division; D002470:Cell Survival; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006728:Hormones / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*
D000906:Antibodies; D006728:Hormones; D016212:Transforming Growth Factor beta; D000254:Sodium-Potassium-Exchanging ATPase