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J Artaza, Internal Medicine/Endocrinology, Charles Drew University, Los Angeles, United States
K Norris, Internal Medicine, Charles Drew University, Los Angeles, United States

Correspondence: Jorge Artaza, Email: jorgeartaza{at}cdrewu.edu

Abstract

Hypovitaminosis D is as an important public health problem. Serum 25-hydroxyvitamin D (25-OHD) is now recognized as an independent predictor for cardiovascular and related diseases (CVD) as well as other chronic medical conditions. However, the biologic pathways through which these effects are mediated remain poorly understood. We hypothesized that exposing mesenchymal multipotent cells to the active form of vitamin D would increase the expression of selected antifibrotic factors that in turn would ameliorate the progression of chronic diseases. Mesenchymal multipotent cells were primed with 5‘-azacytidine to induce a fibrotic phenotype and then treated with active vitamin D (1,25D) or Ethanol < 0.1% as vehicle in a time course manner (30min, 1h, 5h, 24h, 4 days and 7 days). The addition of 1,25D to mesenchymal multipotent cells promotes: a) increased expression and nuclear translocation of the VDR; b) decreased expression of TGF-β1 and PAI-1, two well-known profibrotic factors; c) decreased expression of collagen I, III and other collagens isoforms; and d) increased expression of several antifibrotic factors such as BMP7 a TGF-β1 antagonist, MMP8 a collagen breakdown inducer and follistatin, an inhibitor of the profibrotic factor myostatin. In conclusion, the addition of 1,25D to differentiated mesenchymal multipotent cells displays a decreased profibrotic signaling pathway and gene expression, leading to decrease in collagen deposition. These studies highlight key mechanistic pathways through which vitamin D decrease fibrosis, and provides a rationale for studies to test vitamin D supplementation as a preventive and/or early treatment strategy for CVD and related fibrotic disorders.

This article has been cited by other articles:

				J. N. Artaza, R. Mehrotra, and K. C. Norris Vitamin D and the Cardiovascular System Clin. J. Am. Soc. Nephrol., September 1, 2009; 4(9): 1515 - 1522. [Abstract] [Full Text] [PDF]