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 language | English |
|---|---|
| Pages (from-to) | 737-747 |
| Number of pages | 11 |
| Journal | American Journal of Pathology |
| Volume | 168 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2006 |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Dexamethasone induces connective tissue growth factor expression in renal tubular epithelial cells in a mouse strain-specific manner. / Okada, Hirokazu; Kikuta, Tomohiro; Inoue, Tsutomu; Kanno, Yoshihiko; Ban, Shinichi; Sugaya, Takeshi; Takigawa, Masaharu; Suzuki, Hiromichi.
In: American Journal of Pathology, Vol. 168, No. 3, 03.2006, p. 737-747.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dexamethasone induces connective tissue growth factor expression in renal tubular epithelial cells in a mouse strain-specific manner
AU - Okada, Hirokazu
AU - Kikuta, Tomohiro
AU - Inoue, Tsutomu
AU - Kanno, Yoshihiko
AU - Ban, Shinichi
AU - Sugaya, Takeshi
AU - Takigawa, Masaharu
AU - Suzuki, Hiromichi
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33644643752&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644643752&partnerID=8YFLogxK
U2 - 10.2353/ajpath.2006.050656
DO - 10.2353/ajpath.2006.050656
M3 - Article
C2 - 16507889
AN - SCOPUS:33644643752
VL - 168
SP - 737
EP - 747
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 3
ER -