Autocrine production and TGF-β1-mediated effects on metabolism and viability in renal cells

Grazyna Nowak, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Transforming growth factor-β1 (TGF-β1) 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-β1 treatment stimulated glycolysis before any effect on monolayer DNA content or morphology. TGF-β1 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-β1 decreased oxygen consumption and induced glycolysis but had no effect on morphology and viability of RPTC. Endogenous production of TGF-β1 by RPTC increased 2.6-fold during 10 days of culture. Control RPTC treated with anti-TGF-β antibodies exhibited decreased glycolysis, and lactate metabolism shifted from net production to net consumption. These results show that TGF-β1 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-β antibodies suggests that increased endogenous production of TGF-β is responsible for the stimulation of glycolysis in long-term cultures of RPTC.

Original languageEnglish (US)
Pages (from-to)F689-F697
JournalAmerican Journal of Physiology
Volume271
Issue number3 PART 2
StatePublished - 1996
Externally publishedYes

Keywords

  • Apoptosis
  • Cell death
  • Gluconeogenesis
  • Glycolysis
  • Oxygen consumption
  • Phenotypic transformation of the monolayer
  • Renal proximal tubular cells
  • Sodiumpotassium-adenosinetriphosphatase
  • Transforming growth factor

ASJC Scopus subject areas

  • Physiology (medical)

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