Depletion of miR‐21 in dendritic cells aggravates renal ischemia‐reperfusion injury

Abstract

Dendritic cells (DCs) play an important role in the pathophysiology of renal ischemia‐reperfusion injury (IRI). The mechanisms underlying DCs phenotypic modulation and their function are not fully understood. In this study, we examined the effect of miR‐21 on the phenotypic modulation of DCs in vitro and in vivo, and further investigated the impact of miR‐21‐overexpression DC or miR‐21‐deficient DC on renal IRI. We found that treatment with hypoxia/reoxygenation (H/R) suppressed miR‐21 expression in bone marrow‐derived dendritic cells (BMDCs), and significantly increased the percentage of mature DCs (CD11c+/MHC‐II+/CD80+). Using a selection of microRNA mimics, we successfully induced the upregulation of miR‐21 in BMDCs, which induced immature DC phenotype and an anti‐inflammatory DC response. However, deletion of miR‐21 in BMDCs promoted maturation of DCs under H/R. Adoptive transfer of miR‐21‐overexpression BMDCs could alleviate renal IR‐induced pro‐inflammatory cytokines production and acute kidney injury (AKI). Mice with miR‐21 deficiency in DCs subjected to renal IR showed more severe renal dysfunction and inflammatory response compared with wild‐type mice. In addition, chemokine C receptor 7 (CCR7), a surface marker of mature DC, was a target gene of miR‐21, and silencing of CCR7 in BMDCs led to reduced mature DCs under H/R. In conclusion, our findings highlight miR‐21 as a key regulator of DCs subset phenotype and a potential therapeutic target in renal IRI.

The mechanism of curcumin post-treatment relieving lung injuries by regulating miR-21/TLR4/NF-κB signalling pathway

“…22 Among them, miR-21 is one of the most important because it plays an important role in tumours, cardiovascular disease, immune system diseases, the occurrence and development of epidemic diseases, endocrine diseases and nervous system diseases. 23 Research has shown that the miR-21/ TLR4/NF-jB pathway takes part in myocardial apoptosis in rats with myocardial ischemia-reperfusion. 24 The current study demonstrated that the levels of miR-21 mRNA were significantly increased as a result of ischaemia-reperfusion in rats and treatment with curcumin reduced the levels of miR-21 mRNA.…”

MicroRNAs as Biomarkers and Therapeutic Targets in Inflammation- and Ischemia-Reperfusion-Related Acute Renal Injury

“…The deletion of miR-21 significantly promotes cell death [ 60 ], whereas overexpression of miR-21 suppresses cell death by downregulating programmed cell death protein 4 (PDCD4) in septic AKI [ 61 ]. Additionally, emergent data showed that I/R injury suppressed miR-21 expression in bone marrow-derived dendritic cells, and mice with miR-21 deficiency in dendritic cells aggregated I/R injury [ 62 ]. One clinical study found that miR-21 levels increased both in plasma and urine with increasing AKI severity after adult cardiac surgery [ 63 ].…”

MicroRNA miR-21 Decreases Post-stroke Brain Damage in Rodents

“…The miR-21 is one of the most extensively studied miRNAs. Its expression has been examined in many diseases including various cancers, kidney ischemia, liver ischemia, cardiac ischemia, traumatic brain injury (TBI), and spinal cord injury (SCI) [18,19,[33][34][35][36]. Several of these studies indicate that miR-21 treatment decreases apoptotic and inflammatory burden.…”