In:
Biochemical Journal, Portland Press Ltd., Vol. 362, No. 3 ( 2002-03-15), p. 693-700
Abstract:
Glomerular hypertension has been established as a major factor contributing to glomerular scarring. Underlying cellular mechanisms leading to matrix accumulation are largely unknown. The isolated effect of oscillating hyperbaric pressure [OP; Pmax 50mmHg (1mmHg = 0.133kPa), Pmean 24mmHg, with a fixed oscillation of 60/min] on matrix-degrading protease secretion by rat mesangial cells (MCs) was analysed using a pressure chamber model described previously [Mertens, Espenkott, Venjakob, Heintz, Handt and Sieberth (1998) Hypertension 32, 945–952] . MCs were grown under atmospheric pressure (AP) or a controlled OP, and protease synthesis and gene transcription were analysed. A distinct biphasic cellular response to OP with stimulated gelatinase A protein expression and enzyme activity during the initial 24h, and subsequent inhibition, was apparent, as shown by gelatin zymography. Gelatinase B activity remained unchanged. The abundance of gelatinase A transcripts, determined by reverse transcriptase-PCR, indicated a concordant regulation of gene transcription. To elucidate underlying regu latory events, reporter constructs were transfected. In these experiments, a recently identified response element, RE-1, conferred a significant stimulatory effect within the initial 4h of OP. Nuclear protein/RE-1 binding studies revealed additional complexes from 5min up to 3h after OP exposure, with intensities dependent on Pmax. STAT3 was identified as a component of these novel complexes. Down-regulation of cis-activity after 48h of OP exposure was not transferred via the proximal 1686bp of the gelatinase A regulatory sequence. In conclusion, hyperbaric OP elicits time-dependent changes in rat MC gelatinase A gene transcription.
Type of Medium:
Online Resource
ISSN:
0264-6021
,
1470-8728
Language:
English
Publisher:
Portland Press Ltd.
Publication Date:
2002
detail.hit.zdb_id:
1473095-9
SSG:
12
