Microvesicles from Mesenchymal Stem Cells Overexpressing MiR-34a Ameliorate Renal Fibrosis In Vivo

Abstract

Introduction. We recently discovered that microvesicles (MVs) 
derived from mesenchymal stem cells (MSCs) overexpressing 
miRNA-34a can alleviate experimental kidney injury in mice. In 
this study, we further explored the effects of miR34a-MV on renal 
fibrosis in the unilateral ureteral obstruction (UUO) models. 
Methods. Bone marrow MSCs were modified by lentiviruses 
overexpressing miR-34a, and MVs were collected from the 
supernatants of MSCs. C57BL6/J mice were divided into control, 
unilateral ureteral obstruction (UUO), UUO + MV, UUO + miR-34aMV and UUO + miR-34a-inhibitor-MV groups. MVs were injected 
to mice after surgery. The mice were then euthanized on day 7 
and 14 of modeling, and renal tissues were collected for further 
analyses by Hematoxylin and eosin, Masson’s trichrome, 
and Immunohistochemical (IHC) staining. 
Results. The UUO + MV group exhibited a significantly reduced 
degree of renal interstitial fibrosis with inflammatory cell infiltration, 
tubular epithelial cell atrophy, and vacuole degeneration compared 
with the UUO group. Surprisingly, overexpressing miR-34a enhanced 
these effects of MSC-MV on the UUO mice. 
Conclusion. Our study demonstrates that miR34a further enhances 
the effects of MSC-MV on renal fibrosis in mice through the 
regulation of epithelial-to-mesenchymal transition (EMT) and 
Notch pathway. miR-34a may be a candidate molecular therapeutic 
target for the treatment of renal fibrosis.

DOI: 10.52547/ijkd.7673