TY  - JOUR
A1  - Schäfer, Liliana
A1  - Beck, Karl-Friedrich
A1  - Raslik, Igor
A1  - Walpen, Sebastian
A1  - Mihalik, Daniel
A1  - Mičegová, Miroslava
A1  - Macakova, Katarina
A1  - Schönherr, Elke
A1  - Seidler, Daniela Gabriele
A1  - Varga, Georg
A1  - Schaefer, Roland M.
A1  - Kresse, Hans
A1  - Pfeilschifter, Josef
T1  - Biglycan, a nitric oxide-regulated gene, affects adhesion, growth, and survival of mesangial cells
T2  - Journal of biological chemistry
N2  - During glomerular inflammation mesangial cells are the major source and target of nitric oxide that pro-foundly influences proliferation, adhesion, and death of mesangial cells. The effect of nitric oxide on the mRNA expression pattern of cultured rat mesangial cells was therefore investigated by RNA-arbitrarily-primed polymerase chain reaction. Employing this approach, biglycan expression turned out to be down-regulated time- and dose-dependently either by interleukin-1beta-stimulated endogenous nitric oxide production or by direct application of the exogenous nitric oxide donor, diethylenetriamine nitric oxide. There was a corresponding decline in the rate of biglycan biosynthesis and in the steady state level of this proteoglycan. In vivo, in a model of mesangioproliferative glomerulonephritis up-regulation of inducible nitric-oxide synthase mRNA was associated with reduced expression of biglycan in isolated glomeruli. Biglycan expression could be normalized, both in vitro and in vivo, by using a specific inhibitor of the inducible nitric-oxide synthase, l-N6-(l-iminoethyl)-l-lysine dihydrochloride. Further studies showed that biglycan inhibited cell adhesion on type I collagen and fibronectin because of its binding to these substrates. More importantly, biglycan protected mesangial cells from apoptosis by decreasing caspase-3 activity, and it counteracted the proliferative effects of platelet-derived growth factor-BB. These findings indicate a signaling role of biglycan and describe a novel pathomechanism by which nitric oxide modulates the course of renal glomerular disease through regulation of biglycan expression.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76074
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-760748
SN  - 0021-9258
VL  - 278.2003
IS  - 28
SP  - 26227
EP  - 26237
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -