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Inter‐relationship of fat‐soluble vitamins in progression of renal calcification
Author(s) -
Fu Xueyan,
Mernitz Heather,
Wallin Reidar,
Wang XiangDong,
Booth Sarah L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1106.8
Subject(s) - calcification , endocrinology , chemistry , medicine , matrix gla protein , vitamin , kidney , carcinogenesis , biochemistry , ectopic calcification , cancer
Both 1alpha, 25 dihydroxyvitamin D3 (1,25D, 5.0 μg/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.