Human peripheral blood‑derived exosomes for microRNA delivery

Ji Young Kang, Hyewon Park, Hyoeun Kim, Dasom Mun, Hyelim Park, Nuri Yun, Boyoung Joung

Research output: Contribution to journalArticle

Abstract

Exosomes serve important functions in cell-to-cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood-derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR-21 using a human peripheral blood derived-exosome may influence the degree of remodeling following myocardial infarction (MI). In H9C2 and HL-1 cells, miR-21 expression was successfully regulated by treatment with human peripheral blood derived-exosomes loaded with an miR-21 mimic or inhibitor compared with untreated cells. In addition, the mRNA and protein expression levels of SMAD family member 7 (Smad7), phosphatase and tensin homolog (PTEN) and matrix metalloproteinase 2 (MMP2), which are involved in cardiac fibrosis, were associated with the uptake of miR‑21 mimic‑ or inhibitor-loaded exosomes. Similarly, the in vivo mRNA and protein expression of Smad7, PTEN and MMP2 were altered following treatment with miR-21 mimic- or inhibitor-loaded exosomes. Furthermore, miR-21 mimic-loaded exosomes enhanced fibrosis, whereas miR‑21 inhibitor‑loaded exosomes reduced fibrosis in a mouse MI model. These results suggested that miRNA-loaded human peripheral blood derived-exosomes may be used as a therapeutic tool for cardiac diseases.

Original languageEnglish
Pages (from-to)2319-2328
Number of pages10
JournalInternational journal of molecular medicine
Volume43
Issue number6
DOIs
Publication statusPublished - 2019 Jun

Fingerprint

Exosomes
MicroRNAs
Fibrosis
Matrix Metalloproteinase 2
Phosphoric Monoester Hydrolases
Smad7 Protein
Heart Diseases
Myocardial Infarction
Messenger RNA
Cell Communication

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Kang, Ji Young ; Park, Hyewon ; Kim, Hyoeun ; Mun, Dasom ; Park, Hyelim ; Yun, Nuri ; Joung, Boyoung. / Human peripheral blood‑derived exosomes for microRNA delivery. In: International journal of molecular medicine. 2019 ; Vol. 43, No. 6. pp. 2319-2328.
@article{9a7b7627b49749609d2b23d63a7fc38d,
title = "Human peripheral blood‑derived exosomes for microRNA delivery",
abstract = "Exosomes serve important functions in cell-to-cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood-derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR-21 using a human peripheral blood derived-exosome may influence the degree of remodeling following myocardial infarction (MI). In H9C2 and HL-1 cells, miR-21 expression was successfully regulated by treatment with human peripheral blood derived-exosomes loaded with an miR-21 mimic or inhibitor compared with untreated cells. In addition, the mRNA and protein expression levels of SMAD family member 7 (Smad7), phosphatase and tensin homolog (PTEN) and matrix metalloproteinase 2 (MMP2), which are involved in cardiac fibrosis, were associated with the uptake of miR‑21 mimic‑ or inhibitor-loaded exosomes. Similarly, the in vivo mRNA and protein expression of Smad7, PTEN and MMP2 were altered following treatment with miR-21 mimic- or inhibitor-loaded exosomes. Furthermore, miR-21 mimic-loaded exosomes enhanced fibrosis, whereas miR‑21 inhibitor‑loaded exosomes reduced fibrosis in a mouse MI model. These results suggested that miRNA-loaded human peripheral blood derived-exosomes may be used as a therapeutic tool for cardiac diseases.",
author = "Kang, {Ji Young} and Hyewon Park and Hyoeun Kim and Dasom Mun and Hyelim Park and Nuri Yun and Boyoung Joung",
year = "2019",
month = "6",
doi = "10.3892/ijmm.2019.4150",
language = "English",
volume = "43",
pages = "2319--2328",
journal = "International Journal of Molecular Medicine",
issn = "1107-3756",
publisher = "Spandidos Publications",
number = "6",

}

Human peripheral blood‑derived exosomes for microRNA delivery. / Kang, Ji Young; Park, Hyewon; Kim, Hyoeun; Mun, Dasom; Park, Hyelim; Yun, Nuri; Joung, Boyoung.

In: International journal of molecular medicine, Vol. 43, No. 6, 06.2019, p. 2319-2328.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Human peripheral blood‑derived exosomes for microRNA delivery

AU - Kang, Ji Young

AU - Park, Hyewon

AU - Kim, Hyoeun

AU - Mun, Dasom

AU - Park, Hyelim

AU - Yun, Nuri

AU - Joung, Boyoung

PY - 2019/6

Y1 - 2019/6

N2 - Exosomes serve important functions in cell-to-cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood-derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR-21 using a human peripheral blood derived-exosome may influence the degree of remodeling following myocardial infarction (MI). In H9C2 and HL-1 cells, miR-21 expression was successfully regulated by treatment with human peripheral blood derived-exosomes loaded with an miR-21 mimic or inhibitor compared with untreated cells. In addition, the mRNA and protein expression levels of SMAD family member 7 (Smad7), phosphatase and tensin homolog (PTEN) and matrix metalloproteinase 2 (MMP2), which are involved in cardiac fibrosis, were associated with the uptake of miR‑21 mimic‑ or inhibitor-loaded exosomes. Similarly, the in vivo mRNA and protein expression of Smad7, PTEN and MMP2 were altered following treatment with miR-21 mimic- or inhibitor-loaded exosomes. Furthermore, miR-21 mimic-loaded exosomes enhanced fibrosis, whereas miR‑21 inhibitor‑loaded exosomes reduced fibrosis in a mouse MI model. These results suggested that miRNA-loaded human peripheral blood derived-exosomes may be used as a therapeutic tool for cardiac diseases.

AB - Exosomes serve important functions in cell-to-cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood-derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR-21 using a human peripheral blood derived-exosome may influence the degree of remodeling following myocardial infarction (MI). In H9C2 and HL-1 cells, miR-21 expression was successfully regulated by treatment with human peripheral blood derived-exosomes loaded with an miR-21 mimic or inhibitor compared with untreated cells. In addition, the mRNA and protein expression levels of SMAD family member 7 (Smad7), phosphatase and tensin homolog (PTEN) and matrix metalloproteinase 2 (MMP2), which are involved in cardiac fibrosis, were associated with the uptake of miR‑21 mimic‑ or inhibitor-loaded exosomes. Similarly, the in vivo mRNA and protein expression of Smad7, PTEN and MMP2 were altered following treatment with miR-21 mimic- or inhibitor-loaded exosomes. Furthermore, miR-21 mimic-loaded exosomes enhanced fibrosis, whereas miR‑21 inhibitor‑loaded exosomes reduced fibrosis in a mouse MI model. These results suggested that miRNA-loaded human peripheral blood derived-exosomes may be used as a therapeutic tool for cardiac diseases.

UR - http://www.scopus.com/inward/record.url?scp=85064881497&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064881497&partnerID=8YFLogxK

U2 - 10.3892/ijmm.2019.4150

DO - 10.3892/ijmm.2019.4150

M3 - Article

C2 - 30942393

AN - SCOPUS:85064881497

VL - 43

SP - 2319

EP - 2328

JO - International Journal of Molecular Medicine

JF - International Journal of Molecular Medicine

SN - 1107-3756

IS - 6

ER -