Smad7-dependent regulation of heme oxygenase-1 by transforming growth factor-β in human renal epithelial cells

Nathalie S Hill-kapturczak, Leigh Truong, Vijayalakshmi Thamilselvan, Gary A. Visner, Harry S. Nick, Anupam Agarwal

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Heme oxygenase-1 (HO-1), a 32-kDa microsomal enzyme, is induced as a beneficial and adaptive response in cells/tissues exposed to oxidative stress. Transforming growth factor-β1 (TGF-β1) is a regulatory cytokine that has been implicated in a variety of renal diseases where it promotes extracellular matrix deposition and proinflammatory events. We hypothesize that the release of TGF-β1 via autocrine and/or paracrine pathways may induce HO-1 and serve as a protective response in renal injury. To understand the molecular mechanism of HO-1 induction by TGF-β1, we exposed confluent human renal proximal tubule cells to TGF-β1 and observed a significant induction of HO-1 mRNA at 4 h with a maximal induction at 8 h. This induction was accompanied by increased expression of HO-1 protein. TGF-β1 treatment in conjunction with actinomycin D or cycloheximide demonstrated that induction of HO-1 mRNA requires de novo transcription and, in part, protein synthesis. Exposure to TGF-β1 resulted in marked induction of Smad7 mRNA with no effect on Smad6 expression. Overexpression of Smad7, but not Smad6, inhibited TGF-β1-mediated induction of endogenous HO-1 gene expression. We speculate that the induction of HO-1 in the kidney is an adaptive response to the inflammatory effects of TGF-β1 and manipulations of the Smad pathway to alter HO-1 expression may serve as a potential therapeutic target.

Original languageEnglish (US)
Pages (from-to)40904-40909
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number52
DOIs
StatePublished - Dec 29 2000
Externally publishedYes

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Heme Oxygenase-1
Transforming Growth Factors
Epithelial Cells
Kidney
Messenger RNA
Proximal Kidney Tubule
Oxidative stress
Dactinomycin
Transcription
Cycloheximide
Gene expression
Extracellular Matrix
Proteins
Oxidative Stress
Tissue
Cytokines
Gene Expression
Wounds and Injuries

ASJC Scopus subject areas

  • Biochemistry

Cite this

Hill-kapturczak, N. S., Truong, L., Thamilselvan, V., Visner, G. A., Nick, H. S., & Agarwal, A. (2000). Smad7-dependent regulation of heme oxygenase-1 by transforming growth factor-β in human renal epithelial cells. Journal of Biological Chemistry, 275(52), 40904-40909. https://doi.org/10.1074/jbc.M006621200

Smad7-dependent regulation of heme oxygenase-1 by transforming growth factor-β in human renal epithelial cells. / Hill-kapturczak, Nathalie S; Truong, Leigh; Thamilselvan, Vijayalakshmi; Visner, Gary A.; Nick, Harry S.; Agarwal, Anupam.

In: Journal of Biological Chemistry, Vol. 275, No. 52, 29.12.2000, p. 40904-40909.

Research output: Contribution to journalArticle

Hill-kapturczak, NS, Truong, L, Thamilselvan, V, Visner, GA, Nick, HS & Agarwal, A 2000, 'Smad7-dependent regulation of heme oxygenase-1 by transforming growth factor-β in human renal epithelial cells', Journal of Biological Chemistry, vol. 275, no. 52, pp. 40904-40909. https://doi.org/10.1074/jbc.M006621200
Hill-kapturczak, Nathalie S ; Truong, Leigh ; Thamilselvan, Vijayalakshmi ; Visner, Gary A. ; Nick, Harry S. ; Agarwal, Anupam. / Smad7-dependent regulation of heme oxygenase-1 by transforming growth factor-β in human renal epithelial cells. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 52. pp. 40904-40909.
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