dc.contributor.advisor | Zhou, Beiyan | |
dc.creator | Meng, Cong | |
dc.date.accessioned | 2013-10-03T14:47:09Z | |
dc.date.available | 2013-10-03T14:47:09Z | |
dc.date.created | 2013-05 | |
dc.date.issued | 2013-05-01 | |
dc.date.submitted | May 2013 | |
dc.identifier.uri | https://hdl.handle.net/1969.1/149464 | |
dc.description.abstract | 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.
We have examined the activity of microRNA-223 (miR-223) and its role in controlling macrophage functions in adipose tissue inflammation and systemic insulinresistance. 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 pro-inflammatory pathways and enhances the alternative anti-inflammatory responses. In addition, we identified Pknox1 as a genuine miR-223 target gene and an essential regulator for macrophage polarization.
For the first time, this study demonstrates that miR-223 acts to inhibit Pknox 1,suppressing pro-inflammatory 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. | en |
dc.format.mimetype | application/pdf | |
dc.language.iso | en | |
dc.subject | microRNAs | en |
dc.subject | macrophages | en |
dc.subject | adipose tissue inflammation | en |
dc.title | microRNA-223 Regulates Macrophage Polarization and Diet-induced Insulin Resistance | en |
dc.type | Thesis | en |
thesis.degree.department | Veterinary Physiology and Pharmacology | en |
thesis.degree.discipline | Biomedical Sciences | en |
thesis.degree.grantor | Texas A&M University | en |
thesis.degree.name | Master of Science | en |
thesis.degree.level | Masters | en |
dc.contributor.committeeMember | Wu, Guoyao | |
dc.contributor.committeeMember | Safe, Stephen H | |
dc.type.material | text | en |
dc.date.updated | 2013-10-03T14:47:09Z | |