| First Author | Patel S | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 676752 | PubMed ID | 34394077 |
| Mgi Jnum | J:311511 | Mgi Id | MGI:6762253 |
| Doi | 10.3389/fimmu.2021.676752 | Citation | Patel S, et al. (2021) Characterizing the Role of Glycogen Synthase Kinase-3alpha/beta in Macrophage Polarization and the Regulation of Pro-Atherogenic Pathways in Cultured Ldlr(-/-) Macrophages. Front Immunol 12:676752 |
| abstractText | The molecular and cellular mechanisms that link cardiovascular risk factors to the initiation and progression of atherosclerosis are not understood. Recent findings from our laboratory indicate that endoplasmic reticulum (ER) stress signaling through glycogen synthase kinase (GSK)-3alpha/beta induces pro-atherosclerotic pathways. The objective of this study was to define the specific roles of GSK3alpha and GSK3beta in the activation of pro-atherogenic processes in macrophages. Bone marrow derived macrophages (BMDM) were isolated from low-density lipoprotein receptor knockout (Ldlr(-/-)) mice and Ldlr(-/-) mice with myeloid deficiency of GSK3alpha and/or GSK3beta. M1 and M2 macrophages were used to examine functions relevant to the development of atherosclerosis, including polarization, inflammatory response, cell viability, lipid accumulation, migration, and metabolism. GSK3alpha deficiency impairs M1 macrophage polarization, and reduces the inflammatory response and lipid accumulation, but increases macrophage mobility/migration. GSK3beta deficiency promotes M1 macrophage polarization, which further increases the inflammatory response and lipid accumulation, but decreases macrophage migration. Macrophages deficient in both GSK3alpha and GSK3beta exhibit increased cell viability, proliferation, and metabolism. These studies begin to delineate the specific roles of GSK3alpha and GSK3beta in macrophage polarization and function. These data suggest that myeloid cell GSK3alpha signaling regulates M1 macrophage polarization and pro-atherogenic functions to promote atherosclerosis development. |
