title: Exosome uptake through clathrin-mediated endocytosis and macropinocytosis and mediating miR-21 delivery.
abstract: Exosomes are nanoscale membrane vesicles secreted from many types of cells. Carrying functional molecules, exosomes transfer information between cells and mediate many physiological and pathological processes. In this report, utilizing selective inhibitors, molecular tools, and specific endocytosis markers, the cellular uptake of PC12 cell-derived exosomes was imaged by high-throughput microscopy and statistically analyzed. It was found that the uptake was through clathrin-mediated endocytosis and macropinocytosis. Furthermore, PC12 cell-derived exosomes can enter and deliver microRNAs (miRNAs) into bone marrow-derived mesenchymal stromal cells (BMSCs), and decrease the expression level of transforming growth factor β receptor II (TGFβRII) and tropomyosin-1 (TPM1) through miR-21. These results show the pathway of exosome internalization and demonstrate that tumor cell-derived exosomes regulate target gene expression in normal cells.
authors.affiliation: From the State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China and the Department of Neurobiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: From the State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China and.
authors.forename: Yan-Liang
authors.initials: YL
authors.lastname: Zhu
authors.affiliation: From the State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China and.
authors.forename: Yue-Yuan
authors.initials: YY
authors.lastname: Zhou
authors.affiliation: From the State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China and.
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Liang
authors.affiliation: From the State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China and.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Wang
authors.affiliation: From the State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China and.
authors.forename: Fei-Hu
authors.initials: FH
authors.lastname: Hu
authors.affiliation: From the State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China and zdxiao@seu.edu.cn.
authors.forename: Zhong-Dang
authors.initials: ZD
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D021941:Caveolae / Q000378:metabolism; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D033922:Clathrin Heavy Chains / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034285:Dynamin II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis; D055354:Exosomes / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D016716:PC12 Cells; D010587:Phagocytosis; D010873:Pinocytosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism
chemical_list: C495537:Cav1 protein, rat; D051242:Caveolin 1; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; C490773:Tpm1 protein, rat; D014335:Tropomyosin; C546082:mirn21 microRNA, rat; D033922:Clathrin Heavy Chains; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D034285:Dynamin II
keywords: Cell-Cell Interaction; Endocytosis; Exosome; Extracellular Vesicles; microRNA (miRNA)