Dexamethasone regulates Hox and paraHox gene expression in mouse liver

Abstract

The homeobox (Hox) genes encode homeodomain proteins, which control the development of body forms of many organisms including plants, Drosophila, mouse, and human. Dexamethasone (DEX), a synthetic glucocorticoid with potent anti‐inflammatory effects, can activate pregnane X receptor (PXR) and glucocorticoid receptor (GR) nuclear receptors in a dose‐dependent manner. At low doses such as 2 mg/kg, DEX activates only GR in mouse liver. However, at higher doses such as 50 mg/kg, DEX activates both GR and PXR nuclear receptors. Few studies have reported that DEX can regulate the expression of Hox genes. The purpose of this study was to determine the regulation of Hox (including Hox a‐d subfamily members) and paraHox genes by DEX in mouse liver, as well as the underlying mechanism. Adult male C57BL/6 mice were treated with DEX (2 and 50 mg/kg) once daily for 7 days (n=4–6/treatment). Our results showed that: 1) 2 mg/kg of DEX did not alter mRNA expression of any Hox a–c subfamily members. 2) 50 mg/kg of DEX induced mRNA expression of many Hox a (including Hox a2, a3, a9, a10, a11, and a13), Hox b (including Hox b2, b4, b5, b6, b7, and b9), and Hox c (including Hox c4, c5, c9, c10, c11, and c13) subfamily genes. 3) 2 mg/kg of DEX induced mRNA expression of Hox d9, d11, and d12; whereas 50 mg/kg of DEX induced mRNA expression of Hox d1, d3, d4, d8, d9, d10, d11, and d12. And 4) DEX at the dose of 50 mg/kg but not 2 mg/kg, induced mRNA expression of several other Hox and paraHox genes, including Hex, Pbx1, Gsh1, and Cdx. In conclusion, DEX at the dose of 50 mg/kg but not 2 mg/kg up‐regulated mRNA expression of many Hox and paraHox genes in mouse liver, indicating that signaling of PXR but not GR is involved in Hox and paraHox gene expression.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.