ER stress triggers MCP-1 expression through SET7/9-induced histone methylation in the kidneys of db/db mice.

ER stress triggers MCP-1 expression through SET7/9-induced histone methylation in the kidneys of db/db mice. Am J Physiol Renal Physiol. 2014 Jan 22; Authors: Chen J, Guo Y, Zeng W, Huang L, Pang Q, Nie L, Mu J, Yuan F, Feng B Abstract Epigenetics plays a key role in the pathogenesis of diabetic nephropathy (DN), although the precise regulatory mechanism is still unclear. Here, we examined the role of endoplasmic reticulum (ER) stress in histone H3 lysine 4 (H3K4) methyltransferase SET7/9-induced monocyte chemoattractant protein-1 (MCP-1) expression in the kidneys of db/db mice. Our results indicate that the expression of MCP-1 significantly increased in the kidneys of db/db mice in a time-dependent manner. An increased chromatin mark associated with an active gene (H3K4me1) at MCP-1 promoters accompanied this change in expression. The expression of SET7/9 and the recruitment to these promoters were also elevated. SET7/9 gene silencing with siRNAs significantly attenuated the expression of H3K4me1 and MCP-1. Furthermore, expression of signaling regulator glucose-regulated protein 78 (GRP78), a monitor of ER stress, significantly increased in the kidneys of db/db mice. The expression of ATF6α and spliced X-box binding protein 1 (XBP1s), ER stress-inducible transcription factors, and the recruitment of XBP1s to the SET7/9 promoters were also increased. XBP1s gene silencing with siRNAs significantly attenuated the expression of SET7/9, H3K4me1, ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research