Diabetes Inhibits Gr-1+ Myeloid Cell Maturation via Cebpa Deregulation

Diabetes
Kate WicksKimberly A Mace

Abstract

Recruitment of innate immune cells from the bone marrow (BM) to an injury site is required for effective repair. In diabetes, this process is altered, leading to excessive recruitment and retention of dysfunctional myeloid cells that fail to promote angiogenesis, prolong inflammation, and block healing. The aberrant myeloid phenotype is partially mediated by stable intrinsic changes to developing cells in the BM that are induced by the diabetic (db) environment, but the exact mechanisms remain largely unknown. Here, we show that the db-derived Gr-1(+)CD11b(+) immature myeloid population has widespread misexpression of chromatin-remodeling enzymes and myeloid differentiation factors. Crucially, diabetes represses transcription of the key myeloid transcription factor CEBPA via diminished H3 Lys 27 promoter acetylation, leading to a failure in monocyte and granulocyte maturation. Restoring Cebpa expression by granulocyte colony-stimulating factor reverses the db phenotype and rescues myeloid maturation. Importantly, our data demonstrate a possible link between myeloid cell maturation and chronic inflammation.

References

Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·D E ZhangD G Tenen
Aug 22, 2000·The Journal of Investigative Dermatology·R M DevalarajaA Richmond
Aug 4, 2001·Molecular and Cellular Biology·A H Wang, X J Yang
Feb 21, 2004·The Journal of Biological Chemistry·Feng MiaoRama Natarajan
Jan 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ryan M O'ConnellDavid Baltimore
Jun 6, 2007·Current Diabetes Reports·Michael D Williams, Jerry L Nadler
Feb 29, 2008·Cytokine·Yong-Chen LuPamela S Ohashi
Mar 7, 2008·Development·Eva KutejovaNicoletta Bobola
Mar 28, 2008·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Satoshi IidaRikiro Fukunaga
Nov 14, 2008·International Wound Journal·Jorge Berlanga AcostaGregory S Schultz
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Oct 24, 2009·The American Journal of Pathology·Rita MirzaTimothy J Koh
Nov 10, 2009·Cell Stem Cell·Lars H BussmannThomas Graf
Oct 21, 2010·American Journal of Physiology. Endocrinology and Metabolism·Mohan R Dasu, Ishwarlal Jialal
Mar 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brandt L EsplinPaul W Kincade
Oct 15, 2011·Science Translational Medicine·Francesca FerraroDavid T Scadden
Mar 6, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Tatsuya UsuiHideyuki Yamawaki
Apr 2, 2013·Hematology·Sandhya AnnamaneniMohan Reddy Battini
Jun 24, 2014·Seminars in Immunology·Kate WicksKimberly A Mace

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Citations

Mar 21, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Huichen ZhaoYuantao Liu
Aug 9, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Olga KashpurJonathan A Garlick
Jun 28, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hadeel Al SadounKimberly A Mace

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