Abstract
Previous investigations have demonstrated that growing mesangial cells in high glucose concentration stimulates extracellular matrix synthesis and also increases the expression of TGF-β. We tested whether the stimulation of extracellular matrix production is mediated by autocrine activation of TGF- β, a known prosclerotic cytokine. Addition of neutralizing anti-TGF-β antibody, but not normal rabbit IgG, significantly reduced the high glucose- stimulated incorporation of 3[H]proline. Denaturing SDS-PAGE revealed that mainly collagen types I and IV were stimulated by high (450 mg/dl) D-glucose. This high glucose-mediated increase in collagen synthesis was reduced by the anti-TGF-β antibody. Treatment of mesangial cells grown in normal (100 mg/dl) D-glucose with 2 ng/ml recombinant TGF-β1 mimicked the effects of high glucose. Furthermore, the anti-TGF-β antibody significantly reduced the increase in mRNA levels encoding α2(I) and α1(IV) collagens induced by high glucose. Thus, the high glucose-stimulated increase of collagen production in mesangial cells is mediated, at least in part, by autocrine TGF-β activation. We postulate that the interception of the glomerular activity of TGF-β may be an effective intervention in the management of diabetic nephropathy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 536-542 |
| Number of pages | 7 |
| Journal | Journal of Clinical Investigation |
| Volume | 93 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 1 1994 |
| Externally published | Yes |
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Keywords
- collagen type I
- collagen type IV
- diabetic glomerulopathy
- extracellular matrix
- mouse kidney
ASJC Scopus subject areas
- Medicine(all)
Cite this
Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-β. / Ziyadeh, Fuad N.; Sharma, Kumar; Ericksen, Mark; Wolf, Gunter.
In: Journal of Clinical Investigation, Vol. 93, No. 2, 01.01.1994, p. 536-542.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-β
AU - Ziyadeh, Fuad N.
AU - Sharma, Kumar
AU - Ericksen, Mark
AU - Wolf, Gunter
PY - 1994/1/1
Y1 - 1994/1/1
N2 - Previous investigations have demonstrated that growing mesangial cells in high glucose concentration stimulates extracellular matrix synthesis and also increases the expression of TGF-β. We tested whether the stimulation of extracellular matrix production is mediated by autocrine activation of TGF- β, a known prosclerotic cytokine. Addition of neutralizing anti-TGF-β antibody, but not normal rabbit IgG, significantly reduced the high glucose- stimulated incorporation of 3[H]proline. Denaturing SDS-PAGE revealed that mainly collagen types I and IV were stimulated by high (450 mg/dl) D-glucose. This high glucose-mediated increase in collagen synthesis was reduced by the anti-TGF-β antibody. Treatment of mesangial cells grown in normal (100 mg/dl) D-glucose with 2 ng/ml recombinant TGF-β1 mimicked the effects of high glucose. Furthermore, the anti-TGF-β antibody significantly reduced the increase in mRNA levels encoding α2(I) and α1(IV) collagens induced by high glucose. Thus, the high glucose-stimulated increase of collagen production in mesangial cells is mediated, at least in part, by autocrine TGF-β activation. We postulate that the interception of the glomerular activity of TGF-β may be an effective intervention in the management of diabetic nephropathy.
AB - Previous investigations have demonstrated that growing mesangial cells in high glucose concentration stimulates extracellular matrix synthesis and also increases the expression of TGF-β. We tested whether the stimulation of extracellular matrix production is mediated by autocrine activation of TGF- β, a known prosclerotic cytokine. Addition of neutralizing anti-TGF-β antibody, but not normal rabbit IgG, significantly reduced the high glucose- stimulated incorporation of 3[H]proline. Denaturing SDS-PAGE revealed that mainly collagen types I and IV were stimulated by high (450 mg/dl) D-glucose. This high glucose-mediated increase in collagen synthesis was reduced by the anti-TGF-β antibody. Treatment of mesangial cells grown in normal (100 mg/dl) D-glucose with 2 ng/ml recombinant TGF-β1 mimicked the effects of high glucose. Furthermore, the anti-TGF-β antibody significantly reduced the increase in mRNA levels encoding α2(I) and α1(IV) collagens induced by high glucose. Thus, the high glucose-stimulated increase of collagen production in mesangial cells is mediated, at least in part, by autocrine TGF-β activation. We postulate that the interception of the glomerular activity of TGF-β may be an effective intervention in the management of diabetic nephropathy.
KW - collagen type I
KW - collagen type IV
KW - diabetic glomerulopathy
KW - extracellular matrix
KW - mouse kidney
UR - http://www.scopus.com/inward/record.url?scp=0028218461&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028218461&partnerID=8YFLogxK
U2 - 10.1172/JCI117004
DO - 10.1172/JCI117004
M3 - Article
C2 - 8113392
AN - SCOPUS:0028218461
VL - 93
SP - 536
EP - 542
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 2
ER -