Exosome-encapsulated miR-26a attenuates aldosterone-induced tubulointerstitial fibrosis by inhibiting the CTGF/SMAD3 signaling pathway

Renal tubulointerstitial fibrosis (TIF) is a hallmark in the continuous progression of chronic kidney disease (CKD), in which excessive activation of the renin-angiotensin-aldosterone system serves a crucial role. Currently, there are no targeted therapies for the progression of TIF. microRNA (miR)-26a may be an ideal anti-fibrosis candidate molecule; however, the effect of miR-26 on aldosterone (ALD)-induced TIF remains unclear. This study aimed to elucidate the role of miR-26a in ALD-induced TIF. In the present study, we hypothesized that delivery of miR-26a by exosomes could attenuate ALD-induced TIF. miR-26a expression was downregulated in the kidney of ALD-induced mice compared with the mice in the sham group. Exosome-encapsulated miR-26a (Exo-miR-26a) was manufactured and injected into ALD-treated mice through the tail vein. In vivo experiments showed that Exo-miR-26a alleviated the downregulated miR-26a expression in the kidney, tubular injury and ALD-induced TIF, which was determined using Masson's trichrome staining and assessment of lipocalin 2, α-smooth muscle actin, collagen I and fibronectin expression. Moreover, in vitro experiments revealed that Exo-miR-26a inhibited epithelial-mesenchymal transition and extracellular matrix deposition in mouse tubular epithelial cells. Mechanistically, overexpressing miR-26a led to decreased expression levels of connective tissue growth factor by directly binding to its 3′-UTR and inhibiting the activation of SMAD3. These findings demonstrated that the exosomal delivery of miR-26a may alleviate ALD-induced TIF, which may provide new insights into the treatment of CKD.