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Depletion of miR-21 in Dendritic Cells Aggravates Renal Ischemia-Reperfusion Injury
17 Pages Posted: 20 Nov 2019
More...Abstract
Background: Dendritic cells (DCs) play an important role in the pathophysiology of immune-mediated kidney diseases, including renal ischemia reperfusion injury (IRI). The phenotypic modulation of DCs and their function in ischemia-induced acute kidney injury (AKI) are not fully understood.
Methods: Bone marrow-derived dendritic cells (BMDCs) isolated from mice were treated with hypoxia/reoxygenation (H/R). In vivo, mice were subjected to renal IRI. DC phenotype and pro-inflammatory cytokines expression were analyzed. To examined the effect of miR-21 on DCs phenotype modulation and renal IRI, conditional DC knockout mice were generated and subjected to renal IRI. Adoptive transfer of miR-21-overexpression BMDCs was used to treat IRI mice. Then renal injury were evaluated.
Findings: Treatment with H/R suppressed miR-21 expression in BMDCs, and significantly increased the percentage of mature DCs (CD11c+/MHC-II+/CD80+). Ischemia reperfusion (IR) induced maturation of kidney dendritic subset. Using specific microRNA mimics, we successfully induced the upregulation of miR-21 in BMDCs, which induced immature DC phenotype and an anti-inflammatory DC response. Adoptive transfer of miR-21-overexpression BMDCs alleviated renal IR-induced inflammation and AKI. However, deletion of miR-21 in BMDCs increased the percentage of mature DCs under hypoxia/reoxygenation. Mice with miR-21 deficiency in DCs subjected to renal IR showed more severe renal dysfunction and inflammatory response compared with wild-type mice.
Interpretation: Our findings indicated miR-21 as a critical regulator of DCs subset phenotype. miR-21-deficient DCs displayed a mature phenotype, making mice susceptible to renal IRI. Overexpression of miR-21 in allogenic BMDCs could serve as a therapeutic approach to treat AKI.
Funding Statement: This work was supported by the National Natural Science Foundation of China grants 81430015 (to Xiaoqiang Ding), Science and Technology Commission of Shanghai (14DZ2260200), National Natural Science Foundation of China grants 81670614 (to Xiaoqiang Ding), and 81870466 (to Ping Jia).
Declaration of Interests: The authors declare that they have no conflict of interest.
Ethics Approval Statement: All procedures in this study were approved by the Institutional Animal Care and Use Committee of Fudan University.
Keywords: dendritic cell; ischemia reperfusion injury; miR-21; inflammation
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