Macrophage‐derived exosomal miR‐195a‐5p impairs tubular epithelial cells mitochondria in acute kidney injury mice

Macrophages (Mφ) infiltration is a common characteristic of acute kidney injury (AKI). Exosomes‐mediated cell communication between tubular epithelial cells (TECs) and Mφ has been suggested to be involved in AKI. Exosomes‐derived from injured TECs could regulate Mφ polarization during AKI. However, little is known regarding how activated Mφ regulates kidney injury. To explore the role of activated Mφ in the AKI process, we revealed that Mφ‐derived exosomes from AKI mice (ExosAKI) caused mitochondria damage and induced TECs injury. Then, we detected the global miRNA expression profiles of MφNC and MφAKI and found that among the upregulated miRNAs, miR‐195a‐5p, which regulates mitochondria metabolism in cancer, was significantly increased in MφAKI. Due to the enrichment of miR‐195a‐5p in ExosAKI, the miR‐195a‐5p level in the kidney was elevated in AKI mice. More interestingly, based on the high expression of pri‐miR‐195a‐5p in kidney‐infiltrated Mφ, and the reduction of miR‐195a‐5p in kidney after depletion of Mφ in AKI mice, we confirmed that miR‐195a‐5p may be produced in infiltrated Mφ, and shuttled into TECs via ExosMφ. Furthermore, in vitro inhibition of miR‐195a‐5p alleviated the effect of ExosAKI induced mitochondrial dysfunction and cell injury. Consistently, antagonizing miR‐195a‐5p with a miR‐195a‐5p antagomir attenuated cisplatin‐induced kidney injury and mitochondrial dysfunction in mice. These findings revealed that the Mφ exosomal miR‐195a‐5p derived from AKI mice played a critical pathologic role in AKI progression, representing a new therapeutic target for AKI.