Macrophage Function and the Role of GSK3

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Mar 6

PMID 33672232

Citations 13

Authors

Sarvatit Patel

Geoff H Werstuck

Affiliations

Soon will be listed here.

Abstract

Macrophages are present in nearly all vertebrate tissues, where they respond to a complex variety of regulatory signals to coordinate immune functions involved in tissue development, metabolism, homeostasis, and repair. Glycogen synthase kinase 3 (GSK3) is a ubiquitously expressed protein kinase that plays important roles in multiple pathways involved in cell metabolism. Dysregulation of GSK3 has been implicated in several prevalent metabolic disorders, and recent findings have highlighted the importance of GSK3 activity in the regulation of macrophages, especially with respect to the initiation of specific pathologies. This makes GSK3 a potential therapeutic target for the development of novel drugs to modulate immunometabolic responses. Here, we summarize recent findings that have contributed to our understanding of how GSK3 regulates macrophage function, and we discuss the role of GSK3 in the development of metabolic disorders and diseases.

Citing Articles

The Importance of Phosphoinositide 3-Kinase in Neuroinflammation.

Wright B, King S, Suphioglu C Int J Mol Sci. 2024; 25(21).

PMID: 39519189 PMC: 11546674. DOI: 10.3390/ijms252111638.

Myeloid GSK3α Deficiency Reduces Lesional Inflammation and Neovascularization during Atherosclerotic Progression.

Patel S, Shah N, DMello B, Lee A, Werstuck G Int J Mol Sci. 2024; 25(20).

PMID: 39456687 PMC: 11507289. DOI: 10.3390/ijms252010897.

Notch-1 regulates collective breast cancer cell migration by controlling intercellular junction and cytoskeletal organization.

Zhang Y, Qin X, Guo R, Sun X, Zhao Z, Guo H Cell Prolif. 2024; 58(2):e13754.

PMID: 39343985 PMC: 11839191. DOI: 10.1111/cpr.13754.

Amniotic fluid stem cell-derived extracellular vesicles educate type 2 conventional dendritic cells to rescue autoimmune disorders in a multiple sclerosis mouse model.

Manni G, Gargaro M, Ricciuti D, Fontana S, Padiglioni E, Cipolloni M J Extracell Vesicles. 2024; 13(6):e12446.

PMID: 38844736 PMC: 11156524. DOI: 10.1002/jev2.12446.

Ser9p-GSK3β Modulation Contributes to the Protective Effects of Vitamin C in Neuroinflammation.

Ruggiero M, Cianciulli A, Calvello R, Porro C, De Nuccio F, Kashyrina M Nutrients. 2024; 16(8).

PMID: 38674812 PMC: 11053771. DOI: 10.3390/nu16081121.

References

Colin S, Chinetti-Gbaguidi G, Staels B . Macrophage phenotypes in atherosclerosis. Immunol Rev. 2014; 262(1):153-66. DOI: 10.1111/imr.12218. View

Kanninen K, White A, Koistinaho J, Malm T . Targeting Glycogen Synthase Kinase-3β for Therapeutic Benefit against Oxidative Stress in Alzheimer's Disease: Involvement of the Nrf2-ARE Pathway. Int J Alzheimers Dis. 2011; 2011:985085. PMC: 3100734. DOI: 10.4061/2011/985085. View

Hermida M, Kumar J, Leslie N . GSK3 and its interactions with the PI3K/AKT/mTOR signalling network. Adv Biol Regul. 2017; 65:5-15. DOI: 10.1016/j.jbior.2017.06.003. View

McAlpine C, Huang A, Emdin A, Banko N, Beriault D, Shi Y . Deletion of Myeloid GSK3α Attenuates Atherosclerosis and Promotes an M2 Macrophage Phenotype. Arterioscler Thromb Vasc Biol. 2015; 35(5):1113-22. DOI: 10.1161/ATVBAHA.115.305438. View

Patel S, Doble B, MacAulay K, Sinclair E, Drucker D, Woodgett J . Tissue-specific role of glycogen synthase kinase 3beta in glucose homeostasis and insulin action. Mol Cell Biol. 2008; 28(20):6314-28. PMC: 2577415. DOI: 10.1128/MCB.00763-08. View

Zhang L, Wang Y, Xiao F, Wang S, Xing G, Li Y . CKIP-1 regulates macrophage proliferation by inhibiting TRAF6-mediated Akt activation. Cell Res. 2014; 24(6):742-61. PMC: 4042176. DOI: 10.1038/cr.2014.53. View

Kaidanovich-Beilin O, Woodgett J . GSK-3: Functional Insights from Cell Biology and Animal Models. Front Mol Neurosci. 2011; 4:40. PMC: 3217193. DOI: 10.3389/fnmol.2011.00040. View

Lavine K, Pinto A, Epelman S, Kopecky B, Clemente-Casares X, Godwin J . The Macrophage in Cardiac Homeostasis and Disease: JACC Macrophage in CVD Series (Part 4). J Am Coll Cardiol. 2018; 72(18):2213-2230. PMC: 6209119. DOI: 10.1016/j.jacc.2018.08.2149. View

Guirado E, Schlesinger L, Kaplan G . Macrophages in tuberculosis: friend or foe. Semin Immunopathol. 2013; 35(5):563-83. PMC: 3763202. DOI: 10.1007/s00281-013-0388-2. View

10.

Hoeflich K, Luo J, Rubie E, Tsao M, Jin O, Woodgett J . Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature. 2000; 406(6791):86-90. DOI: 10.1038/35017574. View

11.

Rom S, Fan S, Reichenbach N, Dykstra H, Ramirez S, Persidsky Y . Glycogen synthase kinase 3β inhibition prevents monocyte migration across brain endothelial cells via Rac1-GTPase suppression and down-regulation of active integrin conformation. Am J Pathol. 2012; 181(4):1414-25. PMC: 3463628. DOI: 10.1016/j.ajpath.2012.06.018. View

12.

Yang H, Ye X, Zhang X, Li X, Fu Q, Tang Z . Intracellular osteopontin negatively regulates toll-like receptor 4-mediated inflammatory response via regulating GSK3β and 4EBP1 phosphorylation. Cytokine. 2018; 108:89-95. DOI: 10.1016/j.cyto.2018.03.013. View

13.

Arango Duque G, Descoteaux A . Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol. 2014; 5:491. PMC: 4188125. DOI: 10.3389/fimmu.2014.00491. View

14.

Jain A, Jaiswal A . GSK-3beta acts upstream of Fyn kinase in regulation of nuclear export and degradation of NF-E2 related factor 2. J Biol Chem. 2007; 282(22):16502-10. DOI: 10.1074/jbc.M611336200. View

15.

Kruize Z, Kootstra N . The Role of Macrophages in HIV-1 Persistence and Pathogenesis. Front Microbiol. 2019; 10:2828. PMC: 6906147. DOI: 10.3389/fmicb.2019.02828. View

16.

Beurel E, Jope R . Differential regulation of STAT family members by glycogen synthase kinase-3. J Biol Chem. 2008; 283(32):21934-44. PMC: 2494932. DOI: 10.1074/jbc.M802481200. View

17.

Galvan-Pena S, ONeill L . Metabolic reprograming in macrophage polarization. Front Immunol. 2014; 5:420. PMC: 4151090. DOI: 10.3389/fimmu.2014.00420. View

18.

Woodgett J . Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J. 1990; 9(8):2431-8. PMC: 552268. DOI: 10.1002/j.1460-2075.1990.tb07419.x. View

19.

Ali A, Hoeflich K, Woodgett J . Glycogen synthase kinase-3: properties, functions, and regulation. Chem Rev. 2001; 101(8):2527-40. DOI: 10.1021/cr000110o. View

20.

Nikoulina S, Ciaraldi T, Mudaliar S, Mohideen P, Carter L, Henry R . Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes. Diabetes. 2000; 49(2):263-71. DOI: 10.2337/diabetes.49.2.263. View