ARS | Publication request: Inter-relationship of fat-soluble vitamins in progression of renal calcification

Submitted to: Experimental Biology
Publication Type: Abstract
Publication Acceptance Date: February 1, 2008
Publication Date: April 5, 2008
Citation: Fu, X., Mernitz, H., Wang, X., Wallin, R., Booth, S.L. 2008. Inter-relationship of fat-soluble vitamins in progression of renal calcification. Experimental Biology. FASEB Journal. 22:1106.8.

Technical Abstract: Both 1alpha, 25 dihydroxyvitamin D3 (1,25D, 5.0 ug/kg diet) and 9-cis retinoic acid (9cRA, 15 mg/kg diet) inhibited lung carcinogenesis in a tobacco carcinogen (NNK)-initiated A/J mouse model, but 9cRA mitigated 1,25D-induced renal calcification (Mernitz et al, 2007). Matrix gamma-carboxyglutamic acid protein (MGP) requires vitamin K for gamma-carboxylation, which confers its function as an inhibitor of soft tissue calcification. We therefore hypothesized that fat-soluble vitamins may regulate MGP expression and function. RT-PCR (n=10 per group) and western blotting (n=3 per group) were used to assess MGP expression, and gamma-carboxylation in kidneys of 4 groups of mice: Control (NNK alone), 1,25D (NNK+1,25D), 9cRA (NNK+9cRA) and COMBO (NNK+1,25D+9cRA). Kidney MGP mRNA levels were significantly higher (two-fold) in 1,25D group compared to all other groups (p<0.01). However, there were less carboxylated MGP levels (relative density) in the 1,25D group [1.8+/-1.1 vs. 4.6+/-0.8 (Control); 5.2+/-0.7 (9cRA); 6.5+/-3.2 (COMBO); p<0.05]. In contrast, tissue vitamin K levels (pmol/g) were lowest in the 9cRA and COMBO groups [67+/-32 (Control); 63+/-13 (1,25D); 18+/-7 (9cRA); 33+/-14 (COMBO); p<0.01]. Although the role of vitamin K in this process is unclear, these data suggest that 1,25D can induce renal calcification through the impaired carboxylation of MGP, whereas 9cRA protects against it.