| First Author | Wang X | Year | 2024 |
| Journal | FASEB J | Volume | 38 |
| Issue | 23 | Pages | e70251 |
| PubMed ID | 39659245 | Mgi Jnum | J:360136 |
| Mgi Id | MGI:7797665 | Doi | 10.1096/fj.202401834R |
| Citation | Wang X, et al. (2024) MiR-21 suppression in macrophages promotes M2-like polarization and attenuates kidney ischemia-reperfusion injury. FASEB J 38(23):e70251 |
| abstractText | MicroRNA-21 (miR-21) is one of the most frequently upregulated miRNAs in response to kidney ischemia-reperfusion (IR) injury, exhibiting both protective and pathogenic effects depending on the cell type, disease state, and target signaling. In this study, we analyzed the function of miR-21 in various cell types to elucidate its role in ischemia-induced inflammation and acute kidney injury (AKI). Utilizing a mouse model of IR injury, we observed significant upregulation of miR-21 in renal tubular epithelial cells and macrophages following IR. Deletion of miR-21 in macrophages mitigated IR-induced pro-inflammatory cytokine production and AKI. However, conditional deletion of miR-21 in proximal tubules or nonproximal tubules did not protect the kidneys against these effects. Mechanistically, miR-21 inhibition promoted M2-like polarization in macrophages and suppressed M1-like polarization and proinflammatory cytokine production in kidneys. In vitro, miR-21 knockdown in the mouse macrophage cell line Raw246.7 or genetic deletion of miR-21 in bone marrow-derived macrophages (BMDMs) increased the percentage of CD206(+) cells (M2 phenotype) while decreasing the percentage of CD86(+) cells (M1 phenotype) and the expressions of proinflammatory cytokines. Overexpression of miR-21 in Raw264.7 cells reduced the percentage of CD206(+) cells. Furthermore, we demonstrated that signal transducer and activator of transcription 3 (STAT3) was a target gene of miR-21 in macrophages, and miR-21 deletion promoted M2 macrophage polarization via STAT3 activation. In conclusion, miR-21 plays a role in regulating macrophage polarization, and the blockade of miR-21/STAT3 signaling may represent a novel therapeutic strategy for the prevention or treatment of AKI. |
