Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition

Steven Ledbetter, E. Jill Copeland, Douglas Noonan, Gabriel Vogeli, John R. Hassell

Research output: Contribution to journalArticle

Abstract

We examined steady-state levels of mRNA encoding type IV collagen, B1 chain of laminin, and the basement membrane heparan sulfate proteoglycan in the kidney cortex of a mouse model (KKAy) of non-insulin-dependent diabetes. mRNAs encoding laminin B1 and the proteoglycan were unchanged in kidneys taken from diabetic mice with demonstrable basement membrane thickening. mRNA levels for type IV collagen, in contrast, were significantly elevated (2-fold) in diabetic mice concurrent with but not preceding morphologically thickened basement membranes. There was a negative correlation between a ratio of proteoglycan/type IV collagen and levels of albuminuria in the diabetic mice. No correlation was noted with laminin. We also examined the effects of inhibiting the synthesis of thromboxane, a potent vasoconstrictor, on the steady-state levels of type IV collagen in the diabetic mice. Inhibition of thromboxane stopped the progression of albuminuria and prevented an increase in type IV collagen mRNA levels. We conclude that basement membrane thickening in diabetes, a hallmark of diabetic nephropathy, is partly a consequence of an unbalanced increase in the production of type IV collagen. The relative decrease in proteoglycan production may contribute to chronic albuminuria.

Original languageEnglish
Pages (from-to)196-203
Number of pages8
JournalDiabetes
Volume39
Issue number2
Publication statusPublished - Feb 1990

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Collagen Type IV
Thromboxanes
Basement Membrane
Membrane Proteins
Kidney
Messenger RNA
Albuminuria
Laminin
Proteoglycans
Kidney Cortex
Heparan Sulfate Proteoglycans
Diabetic Nephropathies
Vasoconstrictor Agents

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition. / Ledbetter, Steven; Copeland, E. Jill; Noonan, Douglas; Vogeli, Gabriel; Hassell, John R.

In: Diabetes, Vol. 39, No. 2, 02.1990, p. 196-203.

Research output: Contribution to journalArticle

Ledbetter, Steven ; Copeland, E. Jill ; Noonan, Douglas ; Vogeli, Gabriel ; Hassell, John R. / Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition. In: Diabetes. 1990 ; Vol. 39, No. 2. pp. 196-203.
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