20S-hydroxyvitamin D3, noncalcemic product of CYP11A1 action on vitamin D3, exhibits potent antifibrogenic activity in vivo

Journal of Clinical Endocrinology and Metabolism

Volumn 98, Issue 2, 2013, Pages

  Slominski, Andrzej ^a   Janjetovic, Zorica ^a   Tuckey, Robert C ^b   Nguyen, Minh N ^b   Bhattacharya, Keka G ^a   Wang, Jin ^a   Li, Wei ^a   Jiao, Yan ^a   Gu, Weikuan ^a   Brown, Monica ^a   Postlethwaite, Arnold E ^a  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

1,25 HYDROXYVITAMIN D3; 20 HYDROXYVITAMIN D3; 20,23 HYDROXYVITAMIN D3; CALCIUM ION; COLECALCIFEROL; COLECALCIFEROL DERIVATIVE; COLLAGEN; COLLAGEN TYPE 1; COLLAGEN TYPE 1A2; COLLAGEN TYPE 3; COLLAGEN TYPE 3A1; HYALURONAN SYNTHASE 2; HYALURONIC ACID; IMMUNOMODULATING AGENT; MESSENGER RNA; SYNTHETASE; TRANSFORMING GROWTH FACTOR BETA1; UNCLASSIFIED DRUG; 20-HYDROXYVITAMIN D3; CALCIFEDIOL; DRUG DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIFIBROGENIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BLOOD LEVEL; COLLAGEN SYNTHESIS; CONTROLLED STUDY; DOSE RESPONSE; DRUG ACTIVITY; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG POTENCY; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LOW DRUG DOSE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SCLERODERMA; SCLEROSIS; UPREGULATION; ANIMAL; BIOSYNTHESIS; C57BL MOUSE; CELL CULTURE; CELL PROLIFERATION; CYTOLOGY; DISEASE MODEL; FIBROBLAST; METABOLISM; SKIN; SYSTEMIC SCLEROSIS;

ANIMALS; CALCIFEDIOL; CELL PROLIFERATION; CELLS, CULTURED; COLLAGEN; DISEASE MODELS, ANIMAL; FIBROBLASTS; HUMANS; HYALURONIC ACID; MICE; MICE, INBRED C57BL; SCLERODERMA, SYSTEMIC; SKIN;

MLCS; MLOWN;

EID: 84873670999     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2012-3074     Document Type: Article

References (24)

1. Szodoray P, Nakken B, Gaal J, et al. The complex role of vitamin D in autoimmune diseases. Scand J Immunol. 2008;68:261-269.
2. Bikle DD. Vitamin D: newly discovered actions require reconsideration of physiologic requirements. Trends Endocrinol Metab. 2010; 21:375-384.
3. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-281.
4. Varga J, Pasche B. Transforming growth factor β as a therapeutic target in systemic sclerosis. Nat Rev Rheumatol. 2009;5:200-206.
5. Trojanowska M, Varga J. Molecular pathways as novel therapeutic targets in systemic sclerosis. Curr Opin Rheumatol. 2007;19:568-573.
6. Plum LA, DeLuca HF. Vitamin D, disease and therapeutic opportunities. Nat Rev Drug Discov. 2010;9:941-955.
7. Carlberg C, Molnar F, Mourino A. Vitamin D receptor ligands: the impact of crystal structures. Exp Opin Ther Patents. 2012;22:417-435.
8. Guryev O, Carvalho RA, Usanov S, Gilep A, Estabrook RW. A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1). Proc Natl Acad Sci USA. 2003;100:14754-14759.
9. Slominski A, Semak I, Zjawiony J, et al. The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism. FEBS J. 2005;272:4080-4090.
10. Slominski A, Semak I, Wortsman J, et al. An alternative pathway of vitamin D metabolism. Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2. FEBS J. 2006;273:2891-2901.
11. Tuckey RC, Li W, Zjawiony JK, et al. Pathways and products for the metabolism of vitamin D3 by cytochrome P450scc. FEBS J. 2008; 275:2585-2596.
12. Slominski AT, Kim TK, Shehabi HZ, et al. In vivo evidence for a novel pathway of vitamin D3 metabolism initiated by P450scc and modified by CYP27B1. FASEB J. 26(9):3901-3915.
13. Janjetovic Z, Tuckey RC, Nguyen MN, Thorpe EM Jr, Slominski AT. 20,23-Dihydroxyvitamin D3, novel P450scc product, stimulates differentiation and inhibits proliferation and NF-κB activity in human keratinocytes. J Cell Physiol. 2010;223:36-48.
14. Zbytek B, Janjetovic Z, Tuckey RC, et al. 20-Hydroxyvitamin D3, a product of vitamin D3 hydroxylation by cytochrome P450scc, stimulates keratinocyte differentiation. J Invest Dermatol. 2008; 128:2271-2280.
15. Slominski AT, Janjetovic Z, Fuller BE, et al. Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity. PLoS One. 2010;5:e9907.
16. Slominski AT, Kim TK, Janjetovic Z, et al. 20-Hydroxyvitamin D2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells. AmJ Physiol Cell Physiol. 2011;300:C526-C541.
17. Wang J, Slominski A, Tuckey RC, et al. 20-Hydroxyvitamin D3 inhibits proliferation of cancer cells with high efficacy while being non-toxic. Anticancer Res. 2012;32:739-746.
18. Slominski AT, Li W, Bhattacharya SK, et al. Vitamin D analogs 17,20S(OH)2pD and 17,20R(OH)2pD are noncalcemic and exhibit antifibrotic activity. J Invest Dermatol. 2011;131:1167-1169.
19. Postlethwaite AE, Smith GN Jr, Lachman LB, et al. Stimulation of glycosaminoglycan synthesis in cultured human dermal fibroblasts by interleukin 1. Induction of hyaluronic acid synthesis by natural and recombinant interleukin 1s and synthetic interleukin 1α peptide 163-171. J Clin Invest. 1989;83:629-636.
20. Raghow R, Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH. Transforming growth factor-β increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts. J Clin Invest. 1987;79:1285-1288.
21. Takagawa S, Lakos G, Mori Y, Yamamoto T, Nishioka K, Varga J. Sustained activation of fibroblast transforming growth factor-β/Smad signaling in a murine model of scleroderma. J Invest Dertmatol. 2003;121:41-50.
22. Hirose M, Nishino T, Obata Y, et al. 22-Oxacalcitriol prevents progression of peritoneal fibrosis in a mouse model [published online ahead of print October 2, 2012]. Perit Dial Int. doi:10.3747/pdi.2011.00234.
23. Inoue K, Matsui I, Hamano T, et al. Maxacalcitol ameliorates tubulointerstitial fibrosis in obstructed kidneys by recruiting PPM1A/VDR complex to pSmad3. Lab Invest. 2012;92(12):1686-1697.
24. Cutroneo KR. Human SP1 but not human AP1 binding to the TGF-β element in the 5′ flanking region of the rat PROα1(I)Collagen gene. Mol Bio Rep. 3:191-194.