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Updated: Aug 7, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

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Transcriptional activation of transforming growth factor-beta1 in mesangial cell culture by high glucose

B B Hoffman1, K Sharma, Y Zhu

  • 1Penn Center for Molecular Studies of Kidney Diseases, Department of Medicine, University of Pennsylvania, Philadelphia 19104-6144, USA.

Kidney International
|October 10, 1998
PubMed
Abstract

Insights

High glucose significantly increases transforming growth factor-beta1 (TGF-beta1) production and mRNA levels in kidney cells. This occurs mainly by boosting gene transcription, not by increasing mRNA stability.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Endocrinology

Background:

  • Diabetic nephropathy involves transforming growth factor-beta (TGF-beta), a cytokine promoting hypertrophy and fibrosis.
  • Mechanisms linking high glucose to TGF-beta system regulation in kidney cells are not fully understood.

Purpose of the Study:

  • To investigate how high glucose regulates TGF-beta1 expression in cultured murine mesangial cells (MMCs).

Main Methods:

  • MMCs cultured in normal (100 mg/dl) vs. high (450 mg/dl) glucose.
  • Measured TGF-beta1 protein secretion, bioactivity, mRNA levels, and stability.
  • Utilized promoter-reporter assays (CAT) and electrophoretic mobility shift assays (EMSA) to identify glucose-response elements.

Main Results:

  • High glucose (72 hours) increased TGF-beta1 bioactivity by 47% and secretion by 90%.
  • TGF-beta1 mRNA levels nearly doubled (48 hours) without changes in mRNA stability (half-life ~5 hours).
  • Gene transcription rate increased by 73% (24 hours), linked to a specific promoter region (pA835) with a CACGTG element showing increased protein binding.

Conclusions:

  • High glucose stimulates TGF-beta1 protein production and mRNA levels in MMCs.
  • The primary mechanism is enhanced gene transcription, not altered mRNA stability.
  • A putative glucose-response element in the TGF-beta1 promoter may mediate this transcriptional activation.

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