Affiliation:
1. Department of General Surgery The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China Changsha China
2. Department of Pharmacology & Toxicology, Boonshoft School of Medicine Wright State University Dayton USA
3. Department of Hematology the Third Xiangya Hospital of Central South University Changsha China
Abstract
AbstractThe prognosis of multiple myeloma (MM) patients combined with renal insufficiency is poor. Renal fibrosis is an important pathological cause for MM patients combined with renal insufficiency. It is reported that epithelial–mesenchymal transition (EMT) of renal proximal tubular epithelial cells is an important mechanism in renal fibrosis. We speculated that EMT might play an important role in the renal insufficiency of MM with unclear mechanism. MM cells derived exosomes could affect the function of targeted cells by delivering microRNAs (miRNAs). Literature has shown that the expression of miR‐21 is closely related to EMT. In this research, we found that co‐culture of HK‐2 cells (human renal proximal tubular epithelial cells) and exosomes derived from MM cells promoted the EMT of HK‐2 cells, resulting in the down‐regulation of epithelial‐related marker (E‐cadherin), and up‐regulation of stroma‐related marker (Vimentin). Meanwhile, the expression of SMAD7, one of the downstream targets in the TGF‐β signalling pathway, was suppressed and the expression of TGF‐β was increased. After transfecting the inhibitor of miR‐21 in MM cells, the expression of miR‐21 in exosomes secreted by MM cells was significantly decreased, and the co‐culture of these treated exosomes and HK‐2 cells inhibited the EMT of HK‐2 cells. In conclusion, these findings showed that exosomal miR‐21 derived from MM cells could promote renal EMT through targeting TGF‐β/SMAD7 signalling pathway.
Funder
National Natural Science Foundation of China
Subject
Physiology (medical),Pharmacology,Physiology
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