High inorganic phosphate causes DNMT1 phosphorylation and subsequent fibrotic fibroblast activation
2016 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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High inorganic phosphate causes DNMT1 phosphorylation and subsequent fibrotic fibroblast activation
Tan, X.; Xu, X.; Zeisberg, E. M. & Zeisberg, M. (2016)
Biochemical and Biophysical Research Communications, 472(3) pp. 459-464. DOI: https://doi.org/10.1016/j.bbrc.2016.01.077
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- Authors
- Tan, Xiaoying; Xu, X.; Zeisberg, Elisabeth M. ; Zeisberg, Michael
- Abstract
- Phosphate is an essential constituent of critical cellular functions including energy metabolism, nucleic acid synthesis and phosphorylation-dependent cell signaling. Increased plasma phosphate levels are an independent risk factor for lowered life-expectancy as well as for heart and kidney failure. Nevertheless, direct cellular effects of elevated phosphate concentrations within the microenvironment are poorly understood and have been largely neglected in favor of phosphor-regulatory hormones. Because interstitial fibrosis is the common determinant of chronic progressive kidney disease, and because fibroblasts are major mediators of fibrogenesis, we here explored the effect of high extracellular phosphate levels on renal fibroblasts. We demonstrate that high inorganic phosphate directly induces fibrotic fibroblast activation associated with increased proliferative activity, increased expression of alpha-smooth muscle actin and increased synthesis of type I collagen. We further demonstrate that such fibroblast activation is dependent on phosphate influx, aberrant phosphorylation of DNA methyltransferase DNMT1 and aberrant CpG island promoter methylation. In summary, our studies demonstrate that elevated phosphate concentrations induce pro-fibrotic fibroblast activation independent of phospho-regulatory hormones. (C) 2016 Published by Elsevier Inc.
- Issue Date
- 2016
- Journal
- Biochemical and Biophysical Research Communications
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | C01: Epigenetische Kontrolle der Herzfibrose - Working Group
- RG E. Zeisberg (Kardiales Stroma)
RG M. Zeisberg (Renale Fibrogenese) - External URL
- https://sfb1002.med.uni-goettingen.de/production/literature/publications/138
- ISSN
- 1090-2104; 0006-291X