title: A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation.
abstract: BACKGROUND
  Macrophage activation plays a crucial role in regulating adipose tissue inflammation and is a major contributor to the pathogenesis of obesity-associated cardiovascular diseases. On various types of stimuli, macrophages respond with either classic (M1) or alternative (M2) activation. M1- and M2-mediated signaling pathways and corresponding cytokine production profiles are not completely understood. The discovery of microRNAs provides a new opportunity to understand this complicated but crucial network for macrophage activation and adipose tissue function.
  
  
  RESULTS
  We have examined the activity of microRNA-223 (miR-223) and its role in controlling macrophage functions in adipose tissue inflammation and systemic insulin resistance. miR-223(-/-) mice on a high-fat diet exhibited an increased severity of systemic insulin resistance compared with wild-type mice that was accompanied by a marked increase in adipose tissue inflammation. The specific regulatory effects of miR-223 in myeloid cell-mediated regulation of adipose tissue inflammation and insulin resistance were then confirmed by transplantation analysis. Moreover, using bone marrow-derived macrophages, we demonstrated that miR-223 is a novel regulator of macrophage polarization, which suppresses classic proinflammatory pathways and enhances the alternative antiinflammatory responses. In addition, we identified Pknox1 as a genuine miR-223 target gene and an essential regulator for macrophage polarization.
  
  
  CONCLUSIONS
  For the first time, this study demonstrates that miR-223 acts to inhibit Pknox1, suppressing proinflammatory activation of macrophages; thus, it is a crucial regulator of macrophage polarization and protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhuang
authors.forename: Cong
authors.initials: C
authors.lastname: Meng
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Patali S
authors.initials: PS
authors.lastname: Cheruku
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Hang
authors.initials: H
authors.lastname: Xu
authors.forename: Honggui
authors.initials: H
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Evans
authors.forename: Stephen
authors.initials: S
authors.lastname: Safe
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wu
authors.forename: Beiyan
authors.initials: B
authors.lastname: Zhou
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000276:immunology*; D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology*; D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D016764:Cell Polarity / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004041:Dietary Fats / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology*; D007333:Insulin Resistance / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000276:immunology* / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D009765:Obesity / Q000276:immunology*; D011237:Predictive Value of Tests; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D004041:Dietary Fats; D018398:Homeodomain Proteins; C544877:MIRN223 microRNA, mouse; D035683:MicroRNAs; C491412:Pknox1 protein, mouse; D034741:RNA, Small Interfering