Details

Autor(en) / Beteiligte

• LAM, Suzanne
• VAN DER GEEST, Reinier N
• VERHAGEN, Nicole A. M
• VAN NIEUWENHOVEN, Frans A
• BLOM, Ingrid E
• ATEN, Jan
• GOLDSCHMEDING, Roel
• DAHA, Mohamed R
• VAN KOOTEN, Cees

Titel

Connective Tissue Growth Factor and IGF-I Are Produced by Human Renal Fibroblasts and Cooperate in the Induction of Collagen Production by High Glucose

Ist Teil von

• Diabetes (New York, N.Y.), 2003-12, Vol.52 (12), p.2975-2983

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• Connective Tissue Growth Factor and IGF-I Are Produced by Human Renal Fibroblasts and Cooperate in the Induction of Collagen Production by High Glucose Suzanne Lam 1 , Reinier N. van der Geest 1 , Nicole A.M. Verhagen 1 , Frans A. van Nieuwenhoven 2 , Ingrid E. Blom 2 , Jan Aten 3 , Roel Goldschmeding 2 , Mohamed R. Daha 1 and Cees van Kooten 1 1 Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands 2 Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands 3 Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands Address correspondence and reprint requests to Dr. Cees van Kooten, Leiden University Medical Center, Department of Nephrology, C3P, Albinusdreef 2, 2333 ZA Leiden, Netherlands. E-mail: Kooten{at}lumc.nl Abstract Tubulointerstitial fibrosis is an important component in the development of diabetic nephropathy. Various renal cell types, including fibroblasts, contribute to the excessive matrix deposition in the kidney. Although transforming growth factor-β (TGF-β) has been thought to play a major role during fibrosis, other growth factors are also involved. Here we examined the effects of connective tissue growth factor (CTGF) and IGF-I on collagen type I and III production by human renal fibroblasts and their involvement in glucose-induced matrix accumulation. We have demonstrated that both CTGF and IGF-I expressions were increased in renal fibroblasts under hyperglycemic conditions, also in the absence of TGF-β signaling. Although CTGF alone had no effect on collagen secretion, combined stimulation with IGF-I enhanced collagen accumulation. Furthermore, IGF-I also had a synergistic effect with glucose on the induction of collagens. Moreover, we observed a partial inhibition in glucose-induced collagen secretion with neutralizing anti-CTGF antibodies, thereby demonstrating for the first time the involvement of endogenous CTGF in glucose-induced effects in human renal fibroblasts. Therefore, the cooperation between CTGF and IGF-I might be involved in glucose-induced matrix accumulation in tubulointerstitial fibrosis and might contribute to the pathogenesis of diabetic nephropathy. DMEM, Dulbecco’s modified Eagle’s medium ECM, extracellular matrix ELISA, enzyme-linked immunosorbent assay IGFBP, IGF-binding protein mAb, monoclonal antibody OD, optical density TBP, TATA-box binding protein TGF-β, transforming growth factor-β Footnotes Accepted September 21, 2003. Received March 21, 2003. DIABETES