CTRP9 Enhances Efferocytosis in Macrophages via MAPK/Drp1-Mediated Mitochondrial Fission and AdipoR1-Induced Immunometabolism

References

• Arandjelovic S, Ravichandran KS. Phagocytosis of apoptotic cells in homeostasis. Nat Immunol. 2015;16(9):907–917. doi:10.1038/ni.3253
   PubMed Web of Science ®Google Scholar
• Wang Y, Subramanian M, Yurdagul A Jr., et al. Mitochondrial fission promotes the continued clearance of apoptotic cells by macrophages. Cell. 2017;171(2):331–345 e322. doi:10.1016/j.cell.2017.08.041
   PubMed Web of Science ®Google Scholar
• Serasinghe MN, Wieder SY, Renault TT, et al. Mitochondrial division is requisite to RAS-induced transformation and targeted by oncogenic MAPK pathway inhibitors. Mol Cell. 2015;57(3):521–536. doi:10.1016/j.molcel.2015.01.003
   PubMed Web of Science ®Google Scholar
• Quan H, Kim JM, Lee HJ, Lee SH, Choi JI, Bae HB. AICAR enhances the phagocytic ability of macrophages towards apoptotic cells through P38 mitogen activated protein kinase activation independent of AMP-activated protein kinase. PLoS One. 2015;10(5):e0127885. doi:10.1371/journal.pone.0127885
   PubMed Web of Science ®Google Scholar
• De Maeyer RPH, van de Merwe RC, Louie R, et al. Blocking elevated p38 MAPK restores efferocytosis and inflammatory resolution in the elderly. Nat Immunol. 2020;21(6):615–625. doi:10.1038/s41590-020-0646-0
   PubMed Web of Science ®Google Scholar
• Han CZ, Ravichandran KS. Metabolic connections during apoptotic cell engulfment. Cell. 2011;147(7):1442–1445. doi:10.1016/j.cell.2011.12.006
   PubMed Web of Science ®Google Scholar
• Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S. Identification of Tim4 as a phosphatidylserine receptor. Nature. 2007;450(7168):435–439. doi:10.1038/nature06307
   PubMed Web of Science ®Google Scholar
• Xian X, Ding Y, Dieckmann M, et al. LRP1 integrates murine macrophage cholesterol homeostasis and inflammatory responses in atherosclerosis. Elife. 2017;6.
   Web of Science ®Google Scholar
• Park D, Han CZ, Elliott MR, et al. Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. Nature. 2011;477(7363):220–224. doi:10.1038/nature10340
   PubMed Web of Science ®Google Scholar
• Morioka S, Perry JSA, Raymond MH, et al. Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release. Nature. 2018;563(7733):714–718. doi:10.1038/s41586-018-0735-5
   PubMed Web of Science ®Google Scholar
• Yang Y, Li Y, Ma Z, et al. A brief glimpse at CTRP3 and CTRP9 in lipid metabolism and cardiovascular protection. Prog Lipid Res. 2016;64:170–177. doi:10.1016/j.plipres.2016.10.001
   PubMed Web of Science ®Google Scholar
• Yan W, Guo Y, Tao L, et al. C1q/tumor necrosis factor-related protein-9 regulates the fate of implanted mesenchymal stem cells and mobilizes their protective effects against ischemic heart injury via multiple novel signaling pathways. Circulation. 2017;136(22):2162–2177. doi:10.1161/CIRCULATIONAHA.117.029557
   PubMed Web of Science ®Google Scholar
• Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002;8(11):1288–1295. doi:10.1038/nm788
   PubMed Web of Science ®Google Scholar
• Zong H, Ren JM, Young LH, et al. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A. 2002;99(25):15983–15987. doi:10.1073/pnas.252625599
   PubMed Web of Science ®Google Scholar
• Cheng L, Li B, Chen X, et al. CTRP9 induces mitochondrial biogenesis and protects high glucose-induced endothelial oxidative damage via AdipoR1 -SIRT1- PGC-1alpha activation. Biochem Biophys Res Commun. 2016;477(4):685–691. doi:10.1016/j.bbrc.2016.06.120
   PubMed Web of Science ®Google Scholar
• Liu Q, Zhang H, Lin J, et al. C1q/TNF-related protein 9 inhibits the cholesterol-induced vascular smooth muscle cell phenotype switch and cell dysfunction by activating AMP-dependent kinase. J Cell Mol Med. 2017;21(11):2823–2836. doi:10.1111/jcmm.13196
   PubMed Web of Science ®Google Scholar
• Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, et al. Identification and characterization of CTRP9, a novel secreted glycoprotein, from adipose tissue that reduces serum glucose in mice and forms heterotrimers with adiponectin. FASEB J. 2009;23(1):241–258. doi:10.1096/fj.08-114991
   PubMed Web of Science ®Google Scholar
• Zhang P, Huang C, Li J, et al. Globular CTRP9 inhibits oxLDL-induced inflammatory response in RAW 264.7 macrophages via AMPK activation. Mol Cell Biochem. 2016;417(1–2):67–74. doi:10.1007/s11010-016-2714-1
   PubMed Web of Science ®Google Scholar
• Kambara T, Shibata R, Ohashi K, et al. C1q/tumor necrosis factor-related protein 9 protects against acute myocardial injury through an adiponectin receptor I-AMPK-dependent mechanism. Mol Cell Biol. 2015;35(12):2173–2185. doi:10.1128/MCB.01518-14
   PubMed Web of Science ®Google Scholar
• Takemura Y, Ouchi N, Shibata R, et al. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest. 2007;117(2):375–386. doi:10.1172/JCI29709
   PubMed Web of Science ®Google Scholar
• Kiss RS, Elliott MR, Ma Z, Marcel YL, Ravichandran KS. Apoptotic cells induce a phosphatidylserine-dependent homeostatic response from phagocytes. Curr Biol. 2006;16(22):2252–2258. doi:10.1016/j.cub.2006.09.043
   PubMed Web of Science ®Google Scholar
• Pulanco MC, Cosman J, Ho -M-M, et al. Complement protein C1q enhances macrophage foam cell survival and efferocytosis. J Immunol. 2017;198(1):472–480. doi:10.4049/jimmunol.1601445
   PubMed Web of Science ®Google Scholar
• Galvan MD, Hulsebus H, Heitker T, Zeng E, Bohlson SS. Complement protein C1q and adiponectin stimulate Mer tyrosine kinase-dependent engulfment of apoptotic cells through a shared pathway. J Innate Immun. 2014;6(6):780–792. doi:10.1159/000363295
   PubMed Web of Science ®Google Scholar
• Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000;96(5):1723–1732.
   PubMed Web of Science ®Google Scholar
• Vásquez-Trincado C, García-Carvajal I, Pennanen C, et al. Mitochondrial dynamics, mitophagy and cardiovascular disease. J Physiol. 2016;594(3):509–525. doi:10.1113/JP271301
   PubMed Web of Science ®Google Scholar
• Rogers MA, Maldonado N, Hutcheson JD, et al. Dynamin-related protein 1 inhibition attenuates cardiovascular calcification in the presence of oxidative stress. Circ Res. 2017;121(3):220–233. doi:10.1161/CIRCRESAHA.116.310293
   PubMed Web of Science ®Google Scholar
• Kashatus JA, Nascimento A, Myers LJ, et al. Erk2 phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth. Mol Cell. 2015;57(3):537–551. doi:10.1016/j.molcel.2015.01.002
   PubMed Web of Science ®Google Scholar
• Gui C, Ren Y, Chen J, et al. p38 MAPK-DRP1 signaling is involved in mitochondrial dysfunction and cell death in mutant A53T alpha-synuclein model of Parkinson’s disease. Toxicol Appl Pharmacol. 2020;388:114874. doi:10.1016/j.taap.2019.114874
   PubMed Web of Science ®Google Scholar
• Mukundan L, Odegaard JI, Morel CR, et al. PPAR-delta senses and orchestrates clearance of apoptotic cells to promote tolerance. Nat Med. 2009;15(11):1266–1272. doi:10.1038/nm.2048
   PubMed Web of Science ®Google Scholar
• Rőszer T, Menéndez-Gutiérrez MP, Lefterova MI, et al. Autoimmune kidney disease and impaired engulfment of apoptotic cells in mice with macrophage peroxisome proliferator-activated receptor γ or retinoid X receptor α deficiency. J Immunol. 2011;186(1):621–631. doi:10.4049/jimmunol.1002230
   PubMed Web of Science ®Google Scholar
• Yamauchi T, Nio Y, Maki T, et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med. 2007;13(3):332–339. doi:10.1038/nm1557
   PubMed Web of Science ®Google Scholar
• Matsunami T, Sato Y, Ariga S, et al. Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model. Metabolism. 2011;60(6):805–814. doi:10.1016/j.metabol.2010.07.032
   PubMed Web of Science ®Google Scholar