Renal NG2-expressing cells have a macrophage-like phenotype and facilitate renal recovery after ischemic injury.

Pericytes play an important role in the recovery process after ischemic injury of many tissues. Brain pericytes in the peri-infarct area express macrophage markers in response to injury stimuli and are involved in neovascularization. In the kidney, nerve/glial antigen 2 (NG2) pericytes have been found to accumulate after renal injury. These accumulated NG2 cells are not involved in scar formation. However, the role of accumulated NG2 cells in injured kidneys remains unknown. Here, using a reversible ischemia-reperfusion (I/R) model, we found that renal NG2 cells were increased in injured kidneys and expressed macrophage markers (CD11b or F4/80) on after reperfusion. Isolated NG2 cells from I/R kidneys also had phagocytic activity and expressed anti-inflammatory cytokine genes, including mannose receptor and IL-10. These macrophage-like NG2 cells did not likely differentiate into myofibroblasts because they did not increase α-smooth muscle actin expression. Intravenous transfusion of renal NG2 cells isolated from donor mice on after reperfusion into recipient mice on after I/R surgery revealed that NG2 cell-injected mice had lower plasma blood urea nitrogen, reduced kidney injury molecule-1 mRNA expression, ameliorated renal damage, and reduced cellular debris accumulation compared with PBS-injected mice on after reperfusion. In conclusion, these data suggest that renal NG2 cells have an M2 macrophage-like ability and play a novel role in facilitating the recovery process after renal I/R injury. Brain pericytes have macrophage-like activities after injury. However, such properties of pericytes in peripheral tissues have not been investigated. Here, we provide evidence that nerve/glial antigen 2-positive cells increase after renal injury. The population of nerve/glial antigen 2-positive cells, which does not increase expression of myofibroblast-associated gene, express macrophage markers and anti-inflammatory cytokine genes, have phagocytic activity, and play a role in renal recovery after kidney injury.