Human cortical fibroblast responses to high glucose and hypoxia.

Human cortical fibroblast responses to high glucose and hypoxia. Research Abstract Details 

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Human cortical fibroblast responses to high glucose and hypoxia. Abstract Text:

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.

Human cortical fibroblast responses to high glucose and hypoxia. Publishing Authors By Initials

For similar proteins: tissue inhibitor of metalloproteinases research abstracts see: proteins: tissue inhibitor of metalloproteinases research

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Human cortical fibroblast responses to high glucose and hypoxia. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nephron. Physiology

VOLUME: 96

Page Numbers: p121-9

Journal Abbreviation: Nephron Physiol

ISSN: 1660-2137

DAY: 8

MONTH: 04

YEAR: 2004

Human cortical fibroblast responses to high glucose and hypoxia. Information

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LANGUAGE: eng

NlmUniqueID: 101159772

Human cortical fibroblast responses to high glucose and hypoxia. Keywords Mesh Terms:

KEYWORDS: Tissue Inhibitor of Metalloproteinases

MESH TERMS: metabolism

Chemical & Substance for Abstract: Human cortical fibroblast responses to high glucose and hypoxia. Information

Substance Name: Matrix Metalloproteinases

Registry Number: EC 3.4.24.-

Grant and Affiliation Information for Human cortical fibroblast responses to high glucose and hypoxia.

AFFILIATION: Department of Medicine, University of Sydney, Kolling Institute, Royal North Shore Hospital, St. Leonards, NSW, Australia.

Country: Switzerland

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MEDLINETA: Nephron Physiol

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