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Overexpression of Fibronectin Induced by Diabetes or High Glucose: Phenomenon With a Memory
Open accessAbstract
To identify events and mechanisms that might contribute to the poor reversibility of diabetic complications, we examined whether diabetes or high glucose induces changes in gene expression and whether such changes outlast the presence of the metabolic abnormalities. The study focused on fibronectin because the increased amounts of this glycoprotein found in diabetic tissues and thickened basement membranes are as yet unexplained. In streptozotocin-induced diabetic rats, fibronectin mRNA levels were increased to 304 +/- 295% of control (mean +/- SD) in the kidney cortex (P less than 0.02), and to 271 +/- 273% of control in the heart (P less than 0.02), while actin mRNA levels remained unchanged. Elevation of fibronectin mRNA persisted for weeks after restoration of near-normoglycemia. In cultured human endothelial cells, high glucose-induced overexpression of fibronectin and collagen IV remained detectable after replating and multiple cell divisions in the absence of high glucose. Cells shifted to normal-glucose medium after prolonged exposure to high glucose also exhibited a proliferative advantage over cells chronically maintained in normal glucose. Thus, diabetes increases fibronectin expression in tissues that are known targets of the complications, and the effect is not readily reversible. The in vitro studies suggest that hyperglycemia may be responsible for these events through induction of self-perpetuating changes in gene expression.
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“Data from studies of tissues from streptozotocin-induced diabetic rats and also of endothelial cells in culture indicate that glucose-elevated fibronectin expression is not reversed when normal glycaemia is restored (192).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [192]
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Metadata
- Authors
- Roy, S., Sala, R., Cagliero, E., & Lorenzi, M.
- Affiliations
- Eye Research Institute of Retina Foundation, Boston, MA 02114.
- Harvard University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1990-01
- Volume
- 87
- Issue
- 1
- Pages
- 404-408
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC53272
- OpenAlex
- W2043406584
- Cited by
- 409
- References
- 43
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 11 · 2023: 8 · 2022: 11 · 2021: 11 · 2020: 12 · 2019: 13 · 2018: 6 · 2017: 21 · 2016: 12 · 2015: 22 · 2014: 24 · 2013: 18 · 2012: 25
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl036861-03)
- National Heart, Lung, and Blood Institute (HL-36861)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- fibronectin, diabetes mellitus, high glucose, hyperglycemia, diabetes complications, endothelial cells, type IV collagen, renal cortex, heart, basement membrane thickening, streptozotocin-induced diabetes, cell proliferation
- MeSH terms
- Animals, Cells, Cultured, Diabetes Mellitus, Experimental, Endothelium, Vascular, Female, Fibronectins, Gene Expression Regulation, Glucose, Humans, Kidney Cortex, Male, Myocardium, Pregnancy, Rats, Inbred Strains, Reference Values, RNA, Messenger, Transcription, Genetic, Umbilical Veins, Rats
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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