KLF15 regulates endobiotic and xenobiotic metabolism.

Nature Metabolism
Shuxin HanMukesh K Jain

Abstract

Hepatic metabolism and elimination of endobiotics (for example, steroids, bile acids) and xenobiotics (for example, drugs, toxins) is essential for health. While the enzymatic (termed phase I-II) and transport machinery (termed phase III) controlling endobiotic and xenobiotic metabolism (EXM) is known, understanding of molecular nodal points that coordinate EXM function in physiology and disease remains incomplete. Here we show that the transcription factor Kruppel-like factor 15 (KLF15) regulates all three phases of the EXM system by direct and indirect pathways. Unbiased transcriptomic analyses coupled with validation studies in cells, human tissues, and animals, support direct transcriptional control of the EXM machinery by KLF15. Liver-specific deficiency of KLF15 (Li-KO) results in altered expression of numerous phase I-III targets, and renders animals resistant to the pathologic effects of bile acid and acetaminophen toxicity. Furthermore, Li-KO mice demonstrate enhanced degradation and elimination of endogenous steroid hormones, such as testosterone and glucocorticoid, resulting in reduced male fertility and blood glucose levels, respectively. Viral reconstitution of hepatic KLF15 expression in Li-KO mice reverses these ...Continue Reading

References

May 1, 1993·Trends in Biochemical Sciences·P ZimniakY C Awasthi
Dec 10, 2003·Pharmaceutical Research·Charles R YatesPeter W Swaan
Jan 15, 2005·Biochemical and Biophysical Research Communications·Kiyoshi TeshigawaraMasato Kasuga
Nov 23, 2006·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·E S Tien, M Negishi
Jan 24, 2007·Molecular and Cellular Biology·Yong ChengPeijing Jeremy Wang
Apr 4, 2007·Cell Metabolism·Susan GrayMukesh K Jain
May 29, 2007·Journal of Molecular and Cellular Cardiology·Saptarsi M HaldarMukesh K Jain
Aug 10, 2010·Nucleic Acids Research·Julia Yue CuiCurtis D Klaassen
Oct 21, 2010·Physiological Reviews·Beth B McConnell, Vincent W Yang
Mar 3, 2011·Archives of Toxicology·Liam Baird, Albena T Dinkova-Kostova
Sep 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Conor Liston, Wen-Biao Gan
Mar 13, 2012·Cell Metabolism·Darwin JeyarajMukesh K Jain
Apr 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Saptarsi M HaldarMukesh K Jain
Dec 12, 2012·Nature Biotechnology·Cole TrapnellLior Pachter
Jan 19, 2013·Expert Opinion on Drug Metabolism & Toxicology·Xiaojuan ChaiWen Xie
May 12, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Sriram AmbadapadiMargaret O James
Jun 5, 2015·Nature Communications·Sean Shuxin HanMukesh K Jain
Jan 1, 2015·Nuclear Receptor Research·Chandra PrakashBandana Chatterjee
Aug 23, 2016·Cell Reports·Yoshinori TakeuchiHitoshi Shimano

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Citations

Mar 15, 2020·Nature Communications·Ruben BoonCatherine M Verfaillie

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Methods Mentioned

BETA
RNA-seq
immunoprecipitation
PCR
transfection
bile acid assay
ELISA
ChIP
in vitro transcription

Software Mentioned

ImageJ
Cuffdiff
Alggen Promo Promoter Database
Primer Express
Cufflinks
Blast
- primer
STAR Aligner

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