Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial-myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels

Background Renal tubular epithelial-myofibroblast transdifferentiation (EMT) plays a key role in the regulation of renal fibrosis. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) play a crucial role in alleviating renal fibrosis and injury. Additionally, hucMSC-derived exosomes contain numerous microRNAs (miRNAs). However, it is unclear whether mesenchymal stem cells can regulate the transforming growth factor (TGF)-beta 1-induced EMT of human renal tubular epithelial cells (RTECs) through exosomal miRNAs. Method HK-2, a human RTEC line, was co-treated with TGF-beta 1 and hucMSC-derived exosomes. Additionally, TGF-beta 1-treated HK-2 cells were transfected with a miR-335-5p mimic and disintegrin and metalloproteinase domain-containing protein 19 (ADAM19)-overexpression plasmid. miR-335-5p expression and ADAM19 protein and inflammation levels were measured via quantitative reverse transcription polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assays, respectively. Results TGF-beta 1 treatment changed the shape of HK-2 cells from a cobblestone morphology to a long spindle shape, accompanied by an increase in interleukin (IL)-6, tumor necrosis factor-alpha, IL-1 beta, collagen I, collagen III, alpha-smooth muscle actin, vimentin, and N-cadherin protein levels, whereas E-cadherin protein levels were reduced in these HK-2 cells, suggesting that TGF-beta 1 treatment induced the inflammation and EMT of HK-2 cells. HucMSC-exosomes improved the inflammation and EMT phenotype of TGF-beta 1-induced HK-2 cells by transferring miR-335-5p. miR-335-5p was found to bind the ADAM19 3 '-untranslated region to reduce ADAM19 protein levels. Additionally, miR-335-5p improved the inflammation and EMT phenotype of HK-2 cells by reducing ADAM19 protein levels with TGF-beta 1 induction. Conclusions HucMSC-derived exosomal miR-335-5p attenuates the inflammation and EMT of HK-2 cells by reducing ADAM19 protein levels upon TGF-beta 1 induction. This study provides a potential therapeutic strategy and identifies targets for clinically treating renal fibrosis.

Automated summary

HucMSC-derived exosomal miR-335-5p attenuates the inflammation and EMT of HK-2 cells by reducing ADAM19 protein levels upon TGF-beta 1 induction. This study provides a potential therapeutic strategy and identifies targets for clinically treating renal fibrosis.