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Depletion of miR-21 in Dendritic Cells Aggravates Renal Ischemia-Reperfusion Injury

17 Pages Posted: 20 Nov 2019

See all articles by Ping Jia

Ping Jia

Fudan University - Division of Nephrology

Tianyi Pan

Fudan University - Division of Nephrology

Sujuan Xu

Fudan University - Division of Nephrology

Yi Fang

Fudan University - Division of Nephrology

Nana Song

Fudan University - Division of Nephrology

Man Guo

Fudan University - Division of Nephrology

Yiran Liang

Fudan University - Division of Nephrology

Xialian Xu

Fudan University - Division of Nephrology

Xiaoqiang Ding

Fudan University - Division of Nephrology; Shanghai Medical Center of Kidney Disease; Fudan University - Kidney and Dialysis Institute of Shanghai; Kidney and Blood Purification Laboratory; Hemodialysis Quality Control Center; Shanghai Laboratory of Kidney Disease and Dialysis

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

Suggested Citation

Jia, Ping and Pan, Tianyi and Xu, Sujuan and Fang, Yi and Song, Nana and Guo, Man and Liang, Yiran and Xu, Xialian and Ding, Xiaoqiang, Depletion of miR-21 in Dendritic Cells Aggravates Renal Ischemia-Reperfusion Injury (November 15, 2019). Available at SSRN: https://ssrn.com/abstract=3487709 or http://dx.doi.org/10.2139/ssrn.3487709

Ping Jia

Fudan University - Division of Nephrology

China

Tianyi Pan

Fudan University - Division of Nephrology

China

Sujuan Xu

Fudan University - Division of Nephrology

China

Yi Fang

Fudan University - Division of Nephrology

China

Nana Song

Fudan University - Division of Nephrology

China

Man Guo

Fudan University - Division of Nephrology

China

Yiran Liang

Fudan University - Division of Nephrology

China

Xialian Xu

Fudan University - Division of Nephrology

China

Xiaoqiang Ding (Contact Author)

Fudan University - Division of Nephrology ( email )

China

Shanghai Medical Center of Kidney Disease ( email )

China

Fudan University - Kidney and Dialysis Institute of Shanghai ( email )

China

Kidney and Blood Purification Laboratory ( email )

Shanghai
China

Hemodialysis Quality Control Center ( email )

Shanghai
China

Shanghai Laboratory of Kidney Disease and Dialysis ( email )

China