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Dexamethasone differentially regulates renal and duodenal calcium‐processing genes in calbindin‐D9k and ‐D28k knockout mice
Author(s) -
Kim ManHee,
Lee GeunShik,
Jung EuiMan,
Choi KyungChul,
Oh GooTaeg,
Jeung EuiBae
Publication year - 2009
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2008.044339
Subject(s) - endocrinology , medicine , calbindin , calcitriol receptor , trpv6 , duodenum , calcium , knockout mouse , calcium sensing receptor , parathyroid hormone , calcium metabolism , biology , calcium binding protein , downregulation and upregulation , calcitriol , receptor , chemistry , vitamin d and neurology , gene , biochemistry
Glucocorticoids (GCs) appear to downregulate active calcium‐transporting genes in the duodenum, resulting in GC‐induced calcium‐absorbing disorder. In this study, we examined the effects of GCs on calcium‐processing genes in the duodenum and kidney and the compensatory mechanism in calbindin‐D9k ( CaBP‐9k ) and calbindin‐D28k ( CaBP‐28k ) knockout (KO) mice. In the duodenum, we observed compensatory increases in transient receptor potential vanilloid 6 (TRPV6) mRNAs in both calbindin KO mice and CaBP‐9k transcripts in CaBP‐28k KO mice, and their expressions were decreased by addition of a synthetic GC, dexamethasone (Dex, 10 mg kg −1 ). In addition, the expression of plasma membrane calcium ATPase 1b ( PMCA1b ) underwent a compensatory increase in CaBP‐9k KO mice, and was blocked by Dex, while the mRNA level of duodenal sodium‐calcium exchanger 1 was not altered by KO status or Dex. The renal transcriptional levels of TRPV5 in CaBP‐9k KO and CaBP‐9k in CaBP‐28k KO mice were upregulated in a compensatory manner, while the TRPV6 gene was downregulated following treatment with Dex in the kidney of CaBP‐28k KO mice. The immunological location of these duodenal proteins as a primary target of Dex‐involved regulation was not altered by Dex or KO status. To elucidate potential mechanism(s) of Dex‐induced compensatory gene expression, the levels of GC receptor ( GR ), vitamin D receptor ( VDR ) and parathyroid hormone receptor ( PTHR ) mRNA was also measured in these tissues. Duodenal VDR transcripts were induced in a compensatory manner in both types of KO mice, and were decreased by Dex. In addition, serum corticosterone levels in both KO mice were lower than in wild‐type mice. In conclusion, these results suggest that duodenal TRPV6 and CaBP‐9k genes appear to be a primary target for GC‐induced calcium‐absorbing disorder, through direct regulation of duodenal VDR transcription.