Thrombospondin-2 therapy ameliorates experimental glomerulonephritis via inhibition of cell proliferation, inflammation, and TGF-β activation
Daniel C, Wagner A, Hohenstein B, Hugo C (2009)
Publication Type: Journal article
Publication year: 2009
Journal
Book Volume: 297
Pages Range: F1299-F1309
Journal Issue: 5
DOI: 10.1152/ajprenal.00254.2009
Abstract
We recently identified thrombospondin-2 (TSP-2) as an endogenous regulator of matrix remodelling and inflammation in experimental kidney disease by studying TSP-2-deficient mice. In this study, we asked whether systemic TSP-2 overexpression via thigh muscle transfection is able to ameliorate the time course of the anti-Thy1 glomerulonephritis model. After induction of anti-Thy1 nephritis, rats were transfected either with an overexpression plasmid for TSP-2 or lacZ as a control. Biopsies, urine, and blood samples were taken on days 1, 3, and 6 after disease induction. Muscular overexpression of TSP-2 reduced glomerular transforming growth factor (TGF)-β activation and glomerular extracellular matrix formation as determined by collagen IV and fibronectin. In addition, activation of mesangial cells to the myofibroblast-like phenotype was also significantly decreased in TSP-2-overexpressing animals. TSP-2 overexpression inhibited both glomerular endothelial and mesangial cell proliferation, resulting in a reduced glomerular cell number and glomerular tuft area. The inflammatory response, as monitored by T cells and antigen-presenting cells, was reduced significantly by TSP-2 overexpression, but influx of macrophages was unchanged. These data demonstrate TSP-2 as a potential therapeutic agent to inhibit the glomerular proliferative and inflammatory response as well as TGF-β activation and extracellular matrix accumulation in experimental mesangial proliferative glomerulonephritis. Copyright © 2009 the American Physiological Society.
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APA:
Daniel, C., Wagner, A., Hohenstein, B., & Hugo, C. (2009). Thrombospondin-2 therapy ameliorates experimental glomerulonephritis via inhibition of cell proliferation, inflammation, and TGF-β activation. American Journal of Physiology-Renal Physiology, 297(5), F1299-F1309. https://doi.org/10.1152/ajprenal.00254.2009
MLA:
Daniel, Christoph, et al. "Thrombospondin-2 therapy ameliorates experimental glomerulonephritis via inhibition of cell proliferation, inflammation, and TGF-β activation." American Journal of Physiology-Renal Physiology 297.5 (2009): F1299-F1309.
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