期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 103, 期 3-5, 页码 491-496出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2006.11.011
关键词
vitamin D; renal fibrosis; EMT; chronic kidney disease; HGF; TGF-beta
资金
- NIDDK NIH HHS [R01 DK064005, DK 071040, R01 DK061408, R01 DK071040-03, R01 DK064005-02, R01 DK071040, DK 064005, DK 061408, R01 DK061408-05] Funding Source: Medline
Vitamin D, especially its most active metabolite 1,25-dihydroxyvitamin D-3 or calcitriol, is essential in regulating a wide variety of biologic processes. such as calcium homeostasis, immune modulation, cell proliferation and differentiation. Clinical studies show that the circulating level of calcitriol is substantially reduced in patients with chronic renal insufficiency. Administration of active Vitamin D results in significant amelioration of renal dysfunction and fibrotic lesions in various experimental models of chronic kidney diseases. Active Vitamin D elicits its renal protective activity through multiple mechanisms, such as inhibiting renal inflammation, regulating renin-angiotensin system and blocking mesangial cell activation. Recent studies indicate that calcitriol induces anti-fibrotic hepatocyte growth factor expression, which in turn blocks the myofibroblastic activation and matrix production in interstitial fibroblasts. Furthermore, in vivo and in vitro studies demonstrate that active Vitamin D effectively blocks tubular epithelial to mesenchymal transition (EMT), a phenotypic conversion process that plays a central role in the evolution of renal interstitial fibrosis. Together, it is becoming increasingly clear that a high level of active Vitamin D may be obligatory in the maintenance of normal kidney structure and function. Thus, supplementation of active Vitamin D could be a rational strategy for the therapeutics of chronic kidney diseases. (c) 2006 Elsevier Ltd. All rights reserved.
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