Abstract | BACKGROUND: METHODS: A plasmid containing the promoter region of TGF-β1 cloned upstream of the firefly luciferase gene was electroporated into rat aortic smooth muscle, mesangial, and proximal tubule cells. Luciferase activity was measured in cellular extracts from cells cultured in varying concentrations of glucose and glucosamine. RESULTS:
Glucose treatment of all cultured cells led to a time- and dose-dependent stimulation in TGF-β1 transcriptional activity, with high (20 mM) glucose causing a 1.4- to 2.0-fold increase. Glucose stimulation did not occur until after 12 hours and disappeared after 72 hours of treatment. Glucosamine was more potent than glucose, with 3 mM stimulating up to a 4-fold increase in TGFβ1-transcriptional activity. The stimulatory effect of glucosamine was also dose-dependent but was slower to develop and longer lasting than that of glucose. CONCLUSIONS: The metabolism of glucose through the HBP mediates extracellular matrix production, possibly via the stimulation of TGF-β in kidney cells. Hexosamine metabolism therefore, may play a role in the development of diabetic nephropathy.
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Authors | Marc C Daniels, Donald A McClain, Errol D Crook |
Journal | The American journal of the medical sciences
(Am J Med Sci)
Vol. 359
Issue 2
Pg. 79-83
(02 2020)
ISSN: 1538-2990 [Electronic] United States |
PMID | 32039769
(Publication Type: Journal Article)
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Copyright | Copyright © 2019. Published by Elsevier Inc. |
Chemical References |
- Hexosamines
- TGFB1 protein, human
- Transforming Growth Factor beta1
- Glucose
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Topics |
- Animals
- Diabetic Nephropathies
(genetics, metabolism, pathology)
- Extracellular Matrix
(genetics, metabolism, pathology)
- Gene Expression Regulation
(drug effects)
- Glucose
(metabolism, pharmacology)
- Hexosamines
(biosynthesis, genetics)
- Humans
- Kidney Tubules, Proximal
(metabolism, pathology)
- Mesangial Cells
(metabolism, pathology)
- Mice
- Mice, Transgenic
- Rats
- Time Factors
- Transcription, Genetic
(drug effects)
- Transforming Growth Factor beta1
(biosynthesis, genetics)
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