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  • Title: High glucose-induced TGF-beta 1 regulates mesangial production of heparan sulfate proteoglycan.
    Author: Kolm V, Sauer U, Olgemöller B, Schleicher ED.
    Journal: Am J Physiol; 1996 May; 270(5 Pt 2):F812-21. PubMed ID: 8928843.
    Abstract:
    Previous investigations have demonstrated that growing mesangial cells in high glucose concentration stimulates extracellular matrix synthesis and also increases the expression of transforming growth factor-beta (TGF-beta). We examined the effects of hyperglycemia on mesangial proliferation and heparan sulfate proteoglycan (HSPG) and fibronectin production. Prolonged exposure of mesangial cells to increasing glucose concentrations resulted in dose-dependent effects on growth inhibition and stimulation of matrix production. Treatment of mesangial cells with high glucose-conditioned medium or with TGF-beta 1 mimicked the effects of high-glucose incubation. Furthermore, TGF-beta 1 caused a dose-dependent increase in HSPG mRNA levels. The high-glucose effects on mesangial cells were preceded by an increase in total TGF-beta 1 protein. The presence of TGF-beta 1 antisense oligonucleotide attenuated the glucose-mediated effects on mesangial proliferation and matrix production. The data show that even moderately elevated glucose concentrations appear to affect the mesangial cells. The results indicate that 1) TGF-beta 1 protein production is necessary to obtain the high glucose-induced effects and 2) TGF-beta 1 stimulates mesangial HSPG expression and production. Because these effects may be attenuated by oligonucleotides antisense to TGF-beta 1, the results suggest a possible way for effective intervention in TGF-beta-mediated glomerulosclerosis.
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