A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation. Academic Article uri icon

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. METHODS AND 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. CONCLUSION: 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.

published proceedings

  • Circulation

altmetric score

  • 3.25

author list (cited authors)

  • Zhuang, G., Meng, C., Guo, X., Cheruku, P. S., Shi, L., Xu, H., ... Zhou, B.

citation count

  • 303

complete list of authors

  • Zhuang, Guoqing||Meng, Cong||Guo, Xin||Cheruku, Patali S||Shi, Lei||Xu, Hang||Li, Honggui||Wang, Gang||Evans, Ashley R||Safe, Stephen||Wu, Chaodong||Zhou, Beiyan

publication date

  • June 2012