Exosomes containing miR-148a-3p derived from mesenchymal stem cells suppress epithelial-mesenchymal transition in lens epithelial cells.

Abstract

Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is responsible for the development of fibrotic cataracts, which contribute to severe visual impairment. Recent evidence has shown that mesenchymal stem cell-derived exosomes (MSC-Exo) can attenuate EMT in several tissues. However, the effect of MSC-Exo on EMT in LECs (LECs-EMT) has not been determined. In this study, we isolated exosomes from human umbilical cord MSCs (hucMSC-Exo) and evaluated their effect on LECs-EMT both in vitro and in vivo. HucMSC-Exo application significantly suppressed the expression of mesenchymal cell-associated genes while increasing the expression of epithelial cell-associated genes. Cell proliferation and migration of LECs undergoing EMT were inhibited after hucMSC-Exo treatment. The volume of EMT plaques in mice with injury-induced anterior subcapsular cataract (ASC) was significantly reduced in the hucMSC-Exo-treated group. Furthermore, miR-148a-3p was abundant in hucMSC-Exo. After transfection with miR-148a-3p inhibitor, the anti-fibrotic effect of hucMSC-Exo was attenuated in LECs-EMT. A dual-luciferase reporter assay identified PRNP as a direct target gene of miR-148a-3p. Furthermore, we verified that hucMSC-Exo inhibited LECs-EMT through the miR-148a-3p/PRNP axis and the potential downstream ERK signaling pathway. Taken together, our work reveals the inhibitory effect of hucMSC-Exo on LECs-EMT and the underlying mechanism involved, which may provide potential therapeutic options for fibrotic cataracts.