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. 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.