The regulation of macrophage polarization mainly through the cell signaling mediator. As an important nuclear transcription factor, cAMP response element-binding protein (CREB) has many biological effects. Among them, CREB can promote the migration of macrophages to M2 by upregulating IL-10 and arginase-1 Polarization. Knockdown of two cAMP response element binding sites from the C / EBP beta gene promoter blocks the downstream anti-inflammatory genes associated with M2 macrophages. In skeletal muscle injury model, mitogen-activated protein kinase phosphatase-1 (MKP-1) can promote the transformation of M1 macrophages to M2 by down-regulating p38 mitogen-activated protein kinase. Mice deficient in MKP-1 have a significantly diminished ability to repair damaged skeletal muscle. Early trauma, inflammation of the local hypoxia, then hypoxia will also affect the macrophage phenotype and function changes? Studies have shown that hypoxia inducible factor (HIF) does indeed affect macrophage polarization, HIF1α is associated with polarization of M1 macrophages, and HIF2α promotes polarization of M2 macrophages. In addition, the key molecule Akt in the signal transduction pathway is also involved in the polarization of macrophages and is associated with the subtype. When Akt1 is knocked out, macrophages are polarized to M1 and Akt2 knockdown promotes M2 macrophage formation. The exact mechanism by which different subsets of signal transduction molecules affect macrophages toward different types of polarization remains unclear.
During wound healing, M1 and M2 macrophages have significant differences in glucose, amino acids, and iron metabolism when they perform their different functions. M1 macrophages are often associated with acute infections and early inflammation when they rapidly kill invading bacteria and maintain a tissue-localized hypoxic environment, necessitating prompt energy gain through the glycolysis pathway. Type M2 macrophages are involved in the repair and remodeling of post-traumatic tissue and require a sustained supply of energy. Therefore, over a long period of time, the aerobic oxidation of carbohydrates and fatty acid oxidation can provide M2-type macrophages with sufficient energy. Amino acid metabolism and macrophages in different polarization play a different role is also closely related. M1 macrophages inducible nitric oxide synthase (iNOS) expression is up-regulated, it can be L-arginine catalytic nitric oxide (NO), and to kill microbial NO is an important effector molecule. M2 macrophages are highly expressed Arg-1, can catalyze the formation of polyamines to promote cell proliferation and collagen deposition. Recent studies have shown that M1 and M2 macrophages are also significantly different in iron metabolism, and this difference is compatible with their function. M1 macrophages increase intracellular iron levels via ferritin and transferrin. In contrast to M2 macrophages, high levels of transferrin transport iron from the cell to the outside of the cell. It is known that iron is an essential trace element to promote growth, which makes M1 macrophages the main advantage in resisting microorganisms and protecting the wound from infection, whereas M2 macrophages are more conducive to cell proliferation and tissue repair .
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