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

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

Research output: Contribution to journalArticle

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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 2002

Fingerprint

Cell growth
Collagen
Epithelial Cells
Kidney
Growth
Thymidine
Messenger RNA
Cells
Thromboxane A2
Plating
Transient analysis
Angiotensin II
Animals
Genes
Glucose
Wild Animals
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

TGF-β1 is an autocrine mediator of renal tubular epithelial cell growth and collagen IV production. / Grande, Joseph Peter; Warner, Gina M.; Walker, Henry J.; Yusufi, Ahad N K; Cheng, Jingfei; Gray, Catherine E.; Kopp, Jeffrey B.; Nath, Karl A.

In: Experimental Biology and Medicine, Vol. 227, No. 3, 03.2002, p. 171-181.

Research output: Contribution to journalArticle

Grande, JP, Warner, GM, Walker, HJ, Yusufi, ANK, Cheng, J, Gray, CE, Kopp, JB & Nath, KA 2002, 'TGF-β1 is an autocrine mediator of renal tubular epithelial cell growth and collagen IV production', Experimental Biology and Medicine, vol. 227, no. 3, pp. 171-181.
Grande, Joseph Peter ; Warner, Gina M. ; Walker, Henry J. ; Yusufi, Ahad N K ; Cheng, Jingfei ; Gray, Catherine E. ; Kopp, Jeffrey B. ; Nath, Karl A. / TGF-β1 is an autocrine mediator of renal tubular epithelial cell growth and collagen IV production. In: Experimental Biology and Medicine. 2002 ; Vol. 227, No. 3. pp. 171-181.
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