Fig. 1
Macrophage polarization in pathogenesis of CKD. Macrophages are activated by DAMPs, PAMPs or other mediators, differentiated and polarized into distinct phenotypes through activation of TLRs, NLRP3 inflammasomes and other receptors. Macrophages demonstrate dramatically diverse phenotypes in inflammation, injury-repair cycles and fibrosis over time, depending on the nature of stimulator(s) in the local environment, injury type, persistence, severity and reparative condition of the kidney. In the early stages of CKD, pro-inflammatory phenotypes could be the major feature of macrophages. If the injury resolves, macrophages switch to an anti-inflammatory phenotype. If the injury cannot be resolved, M1 macrophages remain and M2 macrophages are reduced and may revert to M1 at the site. The products (e.g. cytokines, metabolites etc) released from activated macrophages can join with original stimulator(s) further modulate macrophage function through genetic or epigenetic regulation. DAMP, damage-associated molecular pattern; ECM, extracellular matrix; MCP-1, Monocyte chemoattractant protein-1; PAMP, pathogen-associated molecular pattern; PO2, Partial pressure of oxygen; MMP, Matrix metallopeptidase; ROS, reactive oxygen species; TCA cycle, tricarboxylic acid; TLR, Toll-like receptor. Solid line arrow, stimulation; dashed line arrow, not confirmed stimulation