Histone H3 Serine 10 Phosphorylation Facilitates Endothelial Activation in Diabetic Kidney Disease

Diabetes
Tamadher A AlghamdiAndrew Advani

Abstract

The posttranslational histone modifications that epigenetically affect gene transcription extend beyond conventionally studied methylation and acetylation patterns. By examining the means by which podocytes influence the glomerular endothelial phenotype, we identified a role for phosphorylation of histone H3 on serine residue 10 (phospho-histone H3Ser10) in mediating endothelial activation in diabetes. Culture media conditioned by podocytes exposed to high glucose caused glomerular endothelial vascular cell adhesion protein 1 (VCAM-1) upregulation and was enriched for the chemokine CCL2. A neutralizing anti-CCL2 antibody prevented VCAM-1 upregulation in cultured glomerular endothelial cells, and knockout of the CCL2 receptor CCR2 diminished glomerular VCAM-1 upregulation in diabetic mice. CCL2/CCR2 signaling induced glomerular endothelial VCAM-1 upregulation through a pathway regulated by p38 mitogen-activated protein kinase, mitogen- and stress-activated protein kinases 1/2 (MSK1/2), and phosphorylation of H3Ser10, whereas MSK1/2 inhibition decreased H3Ser10 phosphorylation at the VCAM1 promoter. Finally, increased phospho-histone H3Ser10 levels were observed in the kidneys of diabetic endothelial nitric oxide synthase knockou...Continue Reading

References

Jan 1, 1991·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·D SeronD O Haskard
Jul 22, 1999·Diabetes Research and Clinical Practice·K InaY Fujikura
Oct 24, 2002·Cardiovascular Research·Martina WerleJörg Kreuzer
Feb 24, 2004·Journal of the American Society of Nephrology : JASN·Simon C SatchellPeter W Mathieson
May 24, 2006·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hiroki OnoKenji Sunagawa
Feb 22, 2008·American Journal of Physiology. Renal Physiology·Federica CollinoGiovanni Camussi
Apr 4, 2009·Kidney & Blood Pressure Research·Alberto Francisco Rubio-GuerraBruno Alfonso Escalante-Acosta
May 8, 2009·American Journal of Physiology. Renal Physiology·Eun Young LeeSheldon Chen
Dec 21, 2010·The Journal of Biological Chemistry·Michael S Simonson, Faramarz Ismail-Beigi
Apr 29, 2011·Diabetes·Rachana ShahMuredach P Reilly
May 4, 2011·Nature Reviews. Nephrology·Juan F Navarro-GonzálezJavier García-Pérez
Oct 6, 2011·The Biochemical Journal·Shaista NaqviJ Simon C Arthur
Dec 15, 2011·The Journal of Molecular Diagnostics : JMD·Fay WangYuling Luo
Sep 22, 2012·Journal of the American Society of Nephrology : JASN·Darren A YuenAndrew Advani
Mar 15, 2013·The Journal of Clinical Investigation·James K Liao
Mar 5, 2014·The Journal of Clinical Investigation·Ilse DaehnErwin P Bottinger
Jul 6, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hannah X ChuChristopher G Sobey
Aug 14, 2015·The Lancet. Diabetes & Endocrinology·Dick de ZeeuwUNKNOWN CCX140-B Diabetic Nephropathy Study Group
Nov 5, 2015·Journal of the American Society of Nephrology : JASN·Ferhan S SiddiqiAndrew Advani
May 22, 2016·Diabetologia·Luigi Gnudi
Jun 29, 2016·Nature Communications·Shawn S BadalFarhad R Danesh
Nov 13, 2017·Diabetologia·Samuel T KeatingAssam El-Osta
Dec 12, 2017·The Journal of Clinical Investigation·Syamantak MajumderAndrew Advani
Feb 27, 2018·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Katherine R TuttleJonathan M Janes
Jun 24, 2018·Cellular and Molecular Life Sciences : CMLS·Veera Ganesh Yerra, Andrew Advani

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Citations

May 6, 2020·International Journal of Molecular Sciences·Ting-Ting Chang, Jaw-Wen Chen
Feb 5, 2021·Frontiers in Endocrinology·Jie Wang AJunlian Gu
Feb 20, 2021·Kidney Medicine·Cindy Lora GilBruno Larrivée
Mar 26, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Beatriz Maria Veloso PereiraKarina Thieme

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