Dexamethasone induces connective tissue growth factor expression in renal tubular epithelial cells in a mouse strain-specific manner

Hirokazu Okada, Tomohiro Kikuta, Tsutomu Inoue, Yoshihiko Kanno, Shinichi Ban, Takeshi Sugaya, Masaharu Takigawa, Hiromichi Suzuki

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Connective tissue growth factor (CTGF), a downstream mediator of transforming growth factor-β1, mediates mesangial cell/fibroblast proliferation and extracellular matrix production by renal cells. Here, we show that renal tubular epithelial cells from patients with minimal change nephritic syndrome produced CTGF after glucocorticoid treatment In addition, the glucocorticoid dexamethasone (DEX) increased CTGF mRNA levels in the kidneys of C57B6 but not SJL mice and produced intermediate CTGF mRNA levels in the kidneys of F1 (C57B6 × SJL) mice, midway between the levels found for parental strains. DEX also increased CTGF mRNA levels in cultured tubular epithelial cells derived from C57B6 (mProx24) but not SJL (MCT) mice via transcriptional up-regulation of CTGF mRNA. Transient transfection experiments using luciferase reporter constructs bearing CTGF promoter fragments revealed that the -897- to -628-bp fragment contained DEX-responsive positive regulatory elements, which were active in mProx24 but not MCT cells. Long-term DEX treatment resulted in fibronectin deposition in the kidneys of C57B6 but not SJL mice, and this effect was inhibited by co-administration of CTGF anti-sense oligodeoxynucleotides. Thus, glucocorticoid-induced renal fibrogenesis seems to be influenced by genetic background, with the critical DEX-responsive elements in the -897- to -628-bp region of the CTGF promoter.

Original languageEnglish
Pages (from-to)737-747
Number of pages11
JournalAmerican Journal of Pathology
Volume168
Issue number3
DOIs
Publication statusPublished - Mar 2006

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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