Direct regulation of HOXA10 by 1,25-(OH)2D3 in human myelomonocytic cells and human endometrial stromal cells.

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Du H, Daftary GS, Lalwani SI, Taylor HS

Direct regulation of HOXA10 by 1,25-(OH)2D3 in human myelomonocytic cells and human endometrial stromal cells.

Mol Endocrinol. 2005 Sep;19(9):2222-33. Epub 2005 May 19.

PubMed ID

15905361 [ View in PubMed

]

Abstract

Vitamin D receptor (VDR) and the functionally active form of its ligand, 1,25-(OH)2D3, have been implicated in female reproduction function and myeloid leukemic cell differentiation. HOXA10 is necessary for embryo implantation and fertility, as well as hematopoeitic development. In this study, we identified a direct role of vitamin D in the regulation of HOXA10 in primary human endometrial stromal cells, the human endometrial stromal cell line (HESC), and in the human myelomonocytic cell line, U937. Treatment of primary endometrial stromal cells, or the cell lines HESC and U937 with 1,25-(OH)2D3 increased HOXA10 mRNA and protein expression. VDR mRNA and protein were detected in primary uterine stromal cells as well as HESC and U937 cells. We cloned the HOXA10 upstream regulatory sequence and two putative vitamin D response elements (VDRE) into luciferase reporter constructs and transfected primary stromal cells and HESC. One putative VDRE (P1: -385 to -434 bp upstream of HOXA10) drove reporter gene expression in response to treatment with 1,25-(OH)2D3. In EMSA, VDR demonstrated binding to the HOXA10 VDRE in the presence of 1,25-(OH)2D3. 1,25-(OH)2D3 up-regulates HOXA10 expression by binding VDR and interacting with a VDRE in the HOXA10 regulatory region. Direct regulation of HOXA10 by vitamin D has implications for fertility and myeloid differentiation.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Calcitriol	Homeobox protein Hox-A10	Protein	Humans	Unknown	Not Available	Details