High glucose-induced transforming growth factor [beta]1 regulates
mesangial production of heparan sulfate proteoglycan.
Kolm, Verena, Ulrich Sauer, Bernhard Olgem[diaeresis]oller, and Erwin
D. Schleicher.
Institute for Diabetes Research, Department of Biochemistry,
Academic Hospital of the University of Munich, 80804 M[umlaut]unchen,
Germany
APStracts 2:0208F, 1995.
Previous investigations have demonstrated that growing mesangial cells
in high glucose concentration stimulate extracellular ma-trix
synthesis and also increase 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 concentration resulted in dose-dependent effects
on growth inhibition and stimulation of matrix production. Treatment
of mesangial cells with high glucose conditioned media 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. Presence of TGF-[beta]1 anti-sense
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 i) TGF-[beta]1 protein
production is necessary to obtain the high glucose-induced effects
ii) TGF-[beta]1 stimulates mesangial HSPG expression and production.
Since these effects may be attenuated by oligonucleotides anti-sense
to TGF-[beta]1 the results suggest a possible way for effective
intervention in TGF-[beta] mediated glomerulosclerosis.
Received 22 May 1995; accepted in final form 27 November 1995.
APS Manuscript Number F162-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95