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- Title
Glucose-induced fibronectin and collagen type III expression in renal fibroblasts can occur independent of TGF-β1.
- Authors
Lam, Suzanne; Verhagen, Nicole A.M.; Strutz, Frank; Van Der Pijl, Johan W.; Daha, Mohamed R.; Van Kooten, Cees
- Abstract
Glucose-induced fibronectin and collagen type III expression in renal fibroblasts can occur independent of TGF-β1. Background. Various renal cell types have been shown to contribute to the excessive matrix deposition observed in diabetic nephropathy. The present study examined the effect of high ambient glucose and transforming growth factor-β1 (TGF-β1) on matrix production by human renal fibroblasts. Methods. Human renal fibroblasts (TK173) were used to examine the effects of high glucose and TGF-β1 on fibronectin and collagen type III expression. Stable transfectants were generated of TK173 cells expressing a dominant negative TGF-β type II receptor. Matrix components were measured in enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). Results. Fibronectin secretion by renal fibroblasts was increased upon exposure to high glucose, but with delayed kinetics compared to TGF-β1-induced fibronectin. Exposure to high glucose resulted in an increased secretion of latent TGF-β1. However, treatment with neutralizing pan-specific anti-TGF-β antibodies could not attenuate the effects of glucose. Furthermore, collagen type III was up-regulated by high glucose, but not by TGF-β1. Importantly, fibroblasts expressing a dominant negative TGF-β type II receptor were defective in TGF-β1-induced fibronectin production, whereas glucose-induced fibronectin and collagen type III were unaffected. Conclusions. These data show that in renal fibroblasts exposure to high glucose can increase matrix production independent of endogenous TGF-β1. Although glucose activation is accompanied by an increased production of latent TGF-β1, which can have an important role in vivo, the data suggest involvement of alternative growth factors in the mechanism by which hyperglycemic conditions can modulate matrix accumulation in diabetic nephropathy.
- Subjects
KIDNEYS; GLUCOSE; TRANSFORMING growth factors-beta; FIBROBLASTS; FIBRONECTINS
- Publication
Kidney International, 2003, Vol 63, Issue 3, p878
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2003.00824.x