Research Paper Volume 13, Issue 11 pp 15638—15658
Transfer of exosomal microRNA-203-3p from dendritic cells to bone marrow-derived macrophages reduces development of atherosclerosis by downregulating Ctss in mice
- 1 Department of Cardiology, Yulin First People’s Hospital and The Sixth Affiliated Hospital of Guangxi Medical University, Yulin 537000, P.R. China
- 2 Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University and Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention and Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning 530021, P.R. China
Received: December 17, 2019 Accepted: July 14, 2020 Published: June 2, 2021https://doi.org/10.18632/aging.103842
How to Cite
Copyright: © 2021 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Dendritic cell-derived exosomes have been proven to be efficient adjuvant options for anti-tumor vaccines in cancer immunotherapy. However, their potency in atherosclerosis remains unclear. Here we summarize the association of microRNA-203-3p (miR-203-3p) with dendritic cell-derived exosomes and atherosclerosis. Firstly, dendritic cell-derived exosomes and bone marrow-derived macrophages were isolated, after which expression of miR-203-3p and cathepsin S was determined. After the establishment of atherosclerosis mouse models, gain- and loss-of-function experiments were conducted for the analysis of effects of miR-203-3p and cathepsin S on foam-cell formation, lipid accumulation, collagen deposition and serum total cholesterol. The results found high expression of cathepsin S in atherosclerosis mice and downregulation of miR-203-3p in the serum of atherosclerosis patients and ox-LDL-simulated bone marrow-derived macrophages. Cathepsin S was the target gene of miR-203-3p. miR-203-3p transporting from exosomes to bone marrow-derived macrophages resulted in inhibition of cathepsin S expression and atherosclerosis-related phenotypes in bone marrow-derived macrophages, thus alleviating atherosclerosis in mice, and this process was found to involve the p38/MAPK signaling pathway. These findings provided evidence that the transfer of miR-203-3p by dendritic cell-derived exosomes targeted cathepsin S in bone marrow-derived macrophages to attenuate atherosclerosis progression in mice, serving as a promising clinical target for atherosclerosis.
DC: Dendritic cell; AS: atherosclerosis; GEO: Gene Expression Omnibus; BMDMs: bone marrow-derived macrophages; Ctss: cathepsin S; DCexs: DC-derived exosomes; MAPK: mitogen-activated protein kinase; DEGs: deferentially expressed genes; TC: total cholesterol; LDL: low density lipoprotein; TG: triglyceride; ELISA: enzyme-linked immunosorbent assay; OD: The optical density; FC: free cholesterol; CE: the cholesterol esters; GM-CSF: granulocyte-macrophage colony stimulating factor; FBS: fetal bovine serum; TNF: tumor necrosis factor; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis; LAMP1: lysosomal associated membrane protein 1; NC: negative control; RIP: RNA binding protein immunoprecipitation; RIPA: radio-immunoprecipitation assay; PVDF: polyvinylidene fluoride; ECL: enhanced chemiluminescence; SPF: specific-pathogen-free; HFD: high-fat; HE: Hematoxylin-eosin; DAPI: 6-diamidino-2-phenylindole; HDL: high-density lipoprotein.