TNF-α regulates diabetic macrophage function through the histone acetyltransferase MOF

• DOI: 10.1172/jci.insight.132306
• Publication Date: 2020-02-18T17:01:22Z
• Authors: Aaron D. denDekker; Frank M. Davis; Amrita D. Joshi; Sonya J. Wolf; Ronald Allen; Jay Lipinski; Brenda Nguyen; Joseph Kirma; Dylan Nycz; Jennifer Bermick; Bethany B. Moore; Johann E. Gudjonsson; Steven L. Kunkel; Katherine A. Gall...
• Keywords: Histone acetyltransferase; Acetyltransferases

A critical component of wound healing is the transition from inflammatory phase to proliferation initiate and remodeling wound. Macrophages are for initiation resolution during repair. In diabetes, macrophages display a sustained phenotype in late characterized by elevated production cytokines, such as TNF-α. Previous studies have shown that an altered epigenetic program directs diabetic toward proinflammatory phenotype, contributing phase. Males absent on first (MOF) histone acetyltransferase (HAT) has been be coactivator TNF-α signaling promote NF-κB-mediated gene transcription prostate cancer cell lines. Based MOF's role TNF-α/NF-κB-mediated expression, we hypothesized MOF influences macrophage-mediated inflammation We used myeloid-specific Mof-knockout (Lyz2Cre Moffl/fl) diet-induced obese (DIO) mice determine function healing. MOF-deficient exhibited reduced cytokine expression. Furthermore, found DIO had levels higher acetylated H4K16, primary substrate HAT activity, promoters genes. further identified expression could stimulated treatment with etanercept, FDA-approved inhibitor, improved mice. This report our knowledge define important regulating repair identifies inhibition potential therapy chronic wounds.