TGF-β1 is an autocrine mediator of renal tubular epithelial cell growth and collagen IV production

Joseph P. Grande, Gina M. Warner, Henry J. Walker, Ahad N.K. Yusufi, Jingfei Cheng, Catherine E. Gray, Jeffrey B. Kopp, Karl A. Nath

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31 Scopus citations

Abstract

Recent studies in cultured cells have provided evidence that a variety of pathobiologic stimuli, including high glucose, angiotensin II, and thromboxane A2, trigger a signaling pathway leading to autocrine induction of TGF-β1. TGF-β1 production through this pathway may profoundly affect cell growth, matrix synthesis, and response to injury. This study examines the role of autocrine versus exogenously added TGF-β1 in cellular proliferation and collagen IV production, critical targets of TGF-β1 signaling, using renal cells derived from TGF-β1 knockout (KO) animals or wild-type (WT) controls. Growth of WT and KO cells was assessed by cell counting and [3H]thymidine uptake. Basal and TGF-β1-stimulated collagen production was assessed by Northern and Western blotting; transcriptional activity of the α1(IV) collagen gene was assessed by transient transfection analysis. KO cells grew at a faster rate than WT cells carefully matched for plating density and passage number. This increased growth rate was paralleled by increases in [3H]thymidine uptake. KO cells expressed lower levels of the cell cycle inhibitors p21 and p27 than WT cells. KO cells failed to express TGF-β1, as expected. Basal TGF-β3 mRNA levels were higher in KO cells than in WT cells. WT cells expressed higher basal levels of TGF-β2 mRNA than KO cells. Basal α1(IV) and α2(IV) collagen mRNA and protein expression were significantly lower in KO cells than WT cells. Administration of exogenous TGF-β1 induced collagen IV production in both KO and WT cells. Although basal transcriptional activity of an α1(IV) collagen-CAT construct was lower in KO cells than WT cells, administration of exogenous TGF-β1 was associated with significant increases in transcriptional activity of this construct in both KO and WT cells. These studies provide evidence that autocrine production of TGF-β1 may play a critical role in regulation of growth and basal collagen IV production by renal tubular epithelial cells.

Original languageEnglish (US)
Pages (from-to)171-181
Number of pages11
JournalExperimental Biology and Medicine
Volume227
Issue number3
StatePublished - Mar 1 2002

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Keywords

  • Collagen IV
  • Kidney
  • Proliferation
  • TGF-β1
  • Tubular epithelial cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Grande, J. P., Warner, G. M., Walker, H. J., Yusufi, A. N. K., Cheng, J., Gray, C. E., Kopp, J. B., & Nath, K. A. (2002). TGF-β1 is an autocrine mediator of renal tubular epithelial cell growth and collagen IV production. Experimental Biology and Medicine, 227(3), 171-181.