Aberrant DNA methylation of pregnane X receptor underlies metabolic gene alterations in the diabetic kidney

The research group including Project Associate Professor Takeshi Marumo and Emeritus Professor Toshiro Fujita at Research Center for Advanced Science and Technology, the University of Tokyo and Dr Atsushi Watanabe at Department of Nephrology and Endocrinology, National Defense Medical College have demonstrated that diabetes induces aberrant DNA methylation of nuclear receptor PXR in the kidney.
The paper, entitled "Aberrant DNA methylation of pregnane X receptor underlies metabolic gene alterations in the diabetic kidney", has been published in American Journal of Physiology-Renal Physiology on December 6, 2017.

Recent evidence suggests that epigenetic mechanisms may underlie the irreversible nature of diabetic kidney disease. Epigenetic mechanisms, including DNA methylation, maintain the phenotype of the cells by switching on or off the gene expression. Aberrant DNA methylation causes persistent changes in gene expression, leading to progression of disease. The research group found that diabetes induces aberrant DNA methylation that causes persistent increase in expression of nuclear receptor PXR in the kidney. The group also found that PXR activates RGC32, a fibrotic factor, and PCK1, an enzyme involved in gluconeogenesis, in the kidney. Since expression of PXR in the kidney is increased in patients with chronic kidney disease, aberrant DNA methylation of PXR is likely to stimulate pathways leading to fibrosis and gluconeogenesis through persistent increase in PXR.
These findings suggest that PXR may be a potential target of novel treatment for diabetic kidney disease.

Paper

Aberrant DNA methylation of pregnane X receptor underlies metabolic gene alterations in the diabetic kidney

Atsushi Watanabe, Takeshi Marumo, Wakako Kawarazaki, Mitsuhiro Nishimoto, Nobuhiro Ayuzawa, Kohei Ueda, Daigoro Hirohama, Toshiya Tanaka, Shintaro Yagi, Satoshi Ota, Genta Nagae, Hiroyuki Aburatani, Hiroo Kumagai, and Toshiro Fujita