Effects of elevated glucose levels on interactions of cardiac fibroblasts with the extracellular matrix |
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Authors: | Xiaoyi Zhang James A Stewart Jr Ian D Kane Erin P Massey Dawn O Cashatt Wayne E Carver |
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Institution: | (1) Department of Cell and Developmental Biology and Anatomy, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Building 1, Room B-15, Columbia, SC 29209, USA |
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Abstract: | Exposure of fibroblasts to high glucose levels promotes a fibrotic response characterized by increased expression of extracellular
matrix components including interstitial collagens. Little is known about the effects of glucose levels on other aspects of
fibroblast function. Fibroblasts in the myocardium are surrounded by an extensive extracellular matrix composed predominantly
of type I collagen. Interactions between fibroblasts and the myocardial extracellular matrix are thought to affect heart function
by altering ventricular diastolic properties. The purpose of the present study was to determine the effects of elevated glucose
levels on the interactions between heart fibroblasts and the collagenous extracellular matrix. Studies were performed to determine
the effects of relative glucose levels on the ability of fibroblasts to migrate on and contract a three-dimensional collagenous
substratum. These experiments illustrated that exposure of cardiac fibroblasts to high glucose levels (25 mM) resulted in
decreased migratory activity of fibroblasts on a collagen matrix and decreased fibroblast proliferation. In addition, high
glucose stimulated collagen and collagen-binding integrin expression and contraction of three-dimensional collagen gels by
cardiac fibroblasts. These studies illustrate that altered glucose levels induce important changes in the interactions of
cardiac fibroblasts with the collagenous extracellular matrix.
Xiaoyi Zhang and James A. Stewart, Jr. are co-first authors. |
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Keywords: | Fibroblast Integrin Glucose Fibrosis Collagen Migration |
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