MiR-21 suppression in macrophages promotes M2-like polarization and attenuates kidney ischemia-reperfusion injury.

Autor: Wang X; Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China., Ren T; Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China., Zhang X; Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China., Pan T; Shanghai Medical Association, Shanghai, China., Peng F; Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China., Feng J; Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China., Sun Q; Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China., Song N; Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.; Kidney and Blood Purification Laboratory of Shanghai, Shanghai, China., Ding X; Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.; Kidney and Blood Purification Laboratory of Shanghai, Shanghai, China.; Shanghai Medical Center of Kidney, Shanghai, China.; Kidney and Dialysis Institute of Shanghai, Shanghai, China.; Hemodialysis Quality Control Center of Shanghai, Shanghai, China., Jia P; Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.; Kidney and Blood Purification Laboratory of Shanghai, Shanghai, China.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Dec 15; Vol. 38 (23), pp. e70251.
DOI: 10.1096/fj.202401834R
Abstrakt: 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.
(© 2024 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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