Connective tissue growth factor and igf-I are produced by human renal fibroblasts and cooperate in the induction of collagen production by high glucose.
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-beta (TGF-beta) 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-beta 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.
Lam
Suzanne
S
Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
van der Geest
Reinier N
RN
Verhagen
Nicole A M
NA
van Nieuwenhoven
Frans A
FA
Blom
Ingrid E
IE
Aten
Jan
J
Goldschmeding
Roel
R
Daha
Mohamed R
MR
van Kooten
Cees
C
D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis*; D024061:Collagen Type III / Q000096:biosynthesis*; D055513:Connective Tissue Growth Factor; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D007668:Kidney / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
C526317:CCN2 protein, human; D024042:Collagen Type I; D024061:Collagen Type III; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D007334:Insulin-Like Growth Factor I; D005947:Glucose