The study found that IGF2R regulates "proton re-pathways" that give macrophages anti-inflammatory potential

Wang Ying, a researcher at the Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences, and Shi Yuxuan, a researcher at Science Advances, published a research paper online entitled IGF2R-started proton rechanneling dictates an anti-industry property in macrophages.
the study sheds light on the new mechanism by which insulin-like growth factor 2 (insulin like growth factor 2, IGF2) gives macrophage anti-inflammatory and inflammatory potential by activating insulin-like growth factor 2 receptors (insulin like growth factor 2 receptor, IGF2R) and insulin-like growth factor 1 receptor (IGF1R) to give macrophages the potential to regulate natural immune memory.
2019, the team reported its new findings in stem cell research at Cell Metabolism.
-filled stem cells with low oxygen treatment, preprogrammed macrophages have a tendency to metabolize phosphorylation and determine their anti-inflammatory properties, effectively suppressing autoimmune diseases.
In addition, Dr. Wang Xuefeng of the Institute of Nutrition and Health and others found that the therapeutic effect of IGF2 on autoimmune diseases is closely related to the regulation and dose of macrophages - low-dose IGF2 promotes the formation of anti-inflammatory macrophages to alleviate disease, and high-dose IGF2 is conducive to the formation of inflammatory macrophages and aggravates disease.
Given that IGF2 and IGF2R have a higher affinity than their affinity with IGF1R, the properties of IGF2 bidirectional regulation of autoimmune diseases may be related to their differential activation of IGF1R and IGF2R, for which the researchers The mice with myelin cell condition knock-out IGF1R or IGF2R were constructed, and it was proved that the regulation of IGF2 anti-inflammatory macrophages depended on IGF2R, while its regulation of inflammatory macrophages was mainly dependent on IGF1R.
a series of mechanism studies have shown that low-dose IGF2 prioritizes IGF2R, induces IGF2R to cytonucleal kernel internalization, and in-nuclei IGF2R promotes GSK3 alpha/β in combination with chromatin to activate Dnmt3a expression and maintain The high methylated state of the V-type ATP enzyme-related gene inhibits the expression of V-type ATP enzyme, resulting in limited acidification of lysosomes, and the accumulation of H-plus in the cytokine enters the mitochondrial membrane gap by way of a chemical gradient, promoting phosphorylation and giving macrophage anti-inflammatory memory.
researchers named the process of in vivoization of the H-plus to lysase and into the mitochondrial membrane gap, known as proton rechanneling.
In addition, the study also found that high doses of IGF2 not only combined with IGF2R, but also can quickly activate the IGF1R-AKT signaling pathway, through phosphorylation GSK3 alpha/β and inhibit its function, block proton retransmission, promote aerobic sugar ionization, make macrophages have anti-inflammatory function;
show that natural immunity has a strong immune control ability, maintain the normal body's immune stability, in metabolic diseases, cancer, infection and other aspects play an important role.
the continuity of natural immune regulation and similar memories of adaptive immunity are the focus of academic attention.
The study found that IGF2R targeted activity causes the redralubility mechanism of protons in lysosomes and mitochondrials and their key role in determining macrophage anti-inflammatory properties, and regulates new targets and treatment strategies for understanding natural and autoimmune diseases and inflammatory diseases.
()