Table 1.
Summary of macrophage polarization studies in kidney injury
Factor tested | Injury type | Major findings | Effect on macrophages | Ref |
---|---|---|---|---|
Relaxin | UUO AKI | Relaxin administration lowers TLR4 expression Increased renal function and attenuated injury and fibrosis |
Increased M2 polarization | [74] |
PRDX6 | LPS AKI | PRDX6 overexpression decreased mortality and renal injury by lowering ROS via decreasing p38 MAPK and JNK. | Overall lower macrophage infiltration | [75] |
Gpnmb | IR AKI | Gpnmb is highly expressed in M2. Knocking down Gpnmb results in higher IL-1B and TNFa. Gpmb induces M2 activation via IL-4/STAT6 |
Required for IL-4/STAT6 dependent M2 activation | [76] |
IL-4/IL-13 | DT AKI; IR AKI | IL-4/IL-13 activate JAK3/STAT6 Deletion of IL-4/13 results in worsened fibrosis |
Required for M2a activation | [77] |
EPO | RI AKI | EPO administration increases macrophage polarization reduces macrophage recruitment, increased phenotype switch to M2, repressed M1 and increases Jak2/STAT3/STAT6 pathway | Overall lower macrophage infiltration; higher ratio of M2 activation | [36] |
RA | I/R AKI | RA synthesis (Raldh3) is activated in recruited renal macrophages All-Trans Retinoic Acid reduces post-AKI fibrosis RTEC-specific RAR knockdown results reduces M2 polarization in mice |
RTEC-specific RA required for M2 activation | [34] |
EPO | I/R AKI | EPO administration resulted in increased function Increased expression of Wnt7b, B-Cat, downregulation of miR-21, −214,−210, −199a |
EPO lowers renal macrophage infiltration | [78] |
CSF-1 | I/R AKI | CSF-1 depletion results in reduced M2 polarization, delayed functional, structural recovery, increased fibrosis | Required for M2 polarization | [79] |
GM-CSF | I/R AKI | GM-CSF secreted by RTECs increase STAT5 activation and increases RTEC proliferation | Required for M2 polarization | [24] |
SOCS-3 | RI AKI; I/R AKI | SOCS-3 KO in RTECs resulted in increased proliferation and attenuated injury | Inhibits M2 polarization | [80] |
MSC | RI AKI | Increased renal function and injury attenuation function and injury attenuation. | Increases M2 polarization | [37] |
UUO - unilateral uretral obstruction
LPS - Lipopolysaccharide
DT - diphtheria toxin
RI - Rhabdomyolysis induced
I/R - Ischemia/reperfusion
PRDX6 - Peroxiredoxin 6
Gpnmb - Glycoprotein non-metastatic melanoma protein b
EPO - Erythropoietin
RA - Retinoic Acid
CSF-1 - Colony Stimulating Factor-1
GM-CSF - Granulocyte-macrophage colony-stimulating factor
SOCS-3 - suppressor of cytokine signaling 3
MSC - Mesenchymal Stem Cells