Human cortical fibroblast responses to high glucose and hypoxia

Qi, W, Poronnik, P, Young, B, Jackson, C, Field, M and Pollock, C 2004, 'Human cortical fibroblast responses to high glucose and hypoxia', The Nephron Journals, vol. 96, pp. 121-129.


Document type: Journal Article
Collection: Journal Articles

Title Human cortical fibroblast responses to high glucose and hypoxia
Author(s) Qi, W
Poronnik, P
Young, B
Jackson, C
Field, M
Pollock, C
Year 2004
Journal name The Nephron Journals
Volume number 96
Start page 121
End page 129
Total pages 9
Publisher S. Karger AG
Abstract Background/Aims: Approximately 30% of individuals with diabetes mellitus are susceptible to diabetic nephropathy, whereas ischemic injury uniformly induces renal impairment. As matrix accumulation correlates with progressive renal disease we assessed parameters associated with matrix turnover in response to high glucose ± hypoxia in human cortical fibroblasts (CF). Methods: CF were grown to confluence and exposed to media containing 5 or 25 mmol/l D-glucose for 72 h with or without a superimposed hypoxic insult. Results: High glucose increased cellular protein content (p < 0.05). Combined high glucose and hypoxia induced a further increase in cellular protein content (p < 0.005), suggestive of a synergistic hypertrophic effect. MMP secretion corresponded inversely with changes in TIMP expression. In cell cultures derived from 2/3 of patients, high glucose increased MMP-9 (p < 0.0005) and MMP-2 (p < 0.005) while TIMP-1 was reduced (p = 0.05). In the remaining cell cultures derived from 1/3 of patients, MMP-2 was reduced (p < 0.0001) while TIMP-1 and TIMP-2 were both increased (p < 0.05). In contrast, hypoxia induced uniform reductions in MMP-9 and MMP-2 in both normal and high glucose conditions. High glucose increased the expression of PAI-1 mRNA (p < 0.05) in all patients independent of changes in the MMP-TIMP axis. Conclusions: In summary, variability was observed in the MMP-TIMP axis following exposure to high glucose. In contrast, high glucose uniformly induces PAI-1 expression. Hypoxic insults uniformly reduce matrix breakdown independent of the prevailing glucose conditions.
Subject Cell Physiology
DOI - identifier 10.1159/000077383
ISSN 1660-8151
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