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Research
Fengxiang Zhang
The First Affiliated Hospital of Nanjing Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0125-3926
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Background The purpose of this study was to explore whether exosomes derived from MIF engineered umbilical cord MSCs (ucMSCs) exhibit better cardioprotective effects in a rat model of AMI and the mechanisms underlying it.
Results Exosomes isolated from ucMSCs (MSC-Exo), MIF engineered ucMSCs (MIF-Exo) and MIF down-regulated ucMSCs (siMIF-Exo) were used to investigate cellular protective function in human umbilical vein endothelial cells (HUVECs) and H9C2 cardiomyocytes under hypoxia and serum deprivation (H/SD) and infarcted hearts in rats. Compared with MSC-Exo and siMIF-Exo, MIF-Exo significantly enhanced proliferation, migration and angiogenesis of HUVECs and inhibited H9C2 cardiomyocytes apoptosis under H/SD in vitro; MIF-Exo also significantly inhibited cardiomyocytes apoptosis, reduced fibrosis area and improved cardiac function in infarcted rats in vivo. Exosomal miRNAs sequence and qRT-PCR confirmed miRNA-133a-3p remarkably increased in MIF-Exo. The biological effects of HUVECs and H9C2 cardiomyocytes were attenuated with incubation of MIF-Exo and miR-133a-3p inhibitors. And these effects were accentuated with incubation of siMIF-Exo and miR-133a-3p mimics, followed by p-AKT protein level up-regulated.
Conclusion MIF-Exo enhance the effects on promoting angiogenesis, inhibiting apoptosis, reducing fibrosis and preserving heart function, in vitro and in vivo. The miR-133a-3p and its downstream AKT signal pathway were involved in these biological activities of MIF-Exo.
Keywords
Exosomes, macrophage migration inhibitory factor, ucMSCs, miR-133a-3p, Myocardial infarction
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Peer Review Timeline
CURRENT STATUS: Published
View the published article at Journal of Nanobiotechnology.
No community comments so far
Editorial decision: Accept
On 14 Feb, 2021
Review #2 received
Received 09 Feb, 2021
Reviewer #2 agreed
On 03 Feb, 2021
Reviewers invited
Invitations sent on 24 Jan, 2021
Reviewer #1 agreed
On 24 Jan, 2021
Review #1 received
Received 24 Jan, 2021
Editor assigned
On 21 Jan, 2021
Submission checks complete
On 21 Jan, 2021
Editor invited
On 21 Jan, 2021
Version 1
Posted 07 Dec, 2020
No comments provided
Editorial decision: Major revision
On 22 Dec, 2020
Review #2 received
Received 21 Dec, 2020
Review #1 received
Received 11 Dec, 2020
Reviewer #2 agreed
On 02 Dec, 2020
Reviewers invited
Invitations sent on 29 Nov, 2020
Reviewer #1 agreed
On 29 Nov, 2020
Editor invited
On 27 Nov, 2020
Editor assigned
On 27 Nov, 2020
Submission checks complete
On 27 Nov, 2020
First submitted
On 24 Nov, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
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A new preprint design is coming!
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See the published version of this preprint at Journal of Nanobiotechnology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Fengxiang Zhang
The First Affiliated Hospital of Nanjing Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0125-3926
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Journal of Nanobiotechnology.
No community comments so far
Editorial decision: Accept
On 14 Feb, 2021
Review #2 received
Received 09 Feb, 2021
Reviewer #2 agreed
On 03 Feb, 2021
Reviewers invited
Invitations sent on 24 Jan, 2021
Reviewer #1 agreed
On 24 Jan, 2021
Review #1 received
Received 24 Jan, 2021
Editor assigned
On 21 Jan, 2021
Submission checks complete
On 21 Jan, 2021
Editor invited
On 21 Jan, 2021
Version 1
Posted 07 Dec, 2020
No comments provided
Editorial decision: Major revision
On 22 Dec, 2020
Review #2 received
Received 21 Dec, 2020
Review #1 received
Received 11 Dec, 2020
Reviewer #2 agreed
On 02 Dec, 2020
Reviewers invited
Invitations sent on 29 Nov, 2020
Reviewer #1 agreed
On 29 Nov, 2020
Editor invited
On 27 Nov, 2020
Editor assigned
On 27 Nov, 2020
Submission checks complete
On 27 Nov, 2020
First submitted
On 24 Nov, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Journal of Nanobiotechnology.
Background The purpose of this study was to explore whether exosomes derived from MIF engineered umbilical cord MSCs (ucMSCs) exhibit better cardioprotective effects in a rat model of AMI and the mechanisms underlying it.
Results Exosomes isolated from ucMSCs (MSC-Exo), MIF engineered ucMSCs (MIF-Exo) and MIF down-regulated ucMSCs (siMIF-Exo) were used to investigate cellular protective function in human umbilical vein endothelial cells (HUVECs) and H9C2 cardiomyocytes under hypoxia and serum deprivation (H/SD) and infarcted hearts in rats. Compared with MSC-Exo and siMIF-Exo, MIF-Exo significantly enhanced proliferation, migration and angiogenesis of HUVECs and inhibited H9C2 cardiomyocytes apoptosis under H/SD in vitro; MIF-Exo also significantly inhibited cardiomyocytes apoptosis, reduced fibrosis area and improved cardiac function in infarcted rats in vivo. Exosomal miRNAs sequence and qRT-PCR confirmed miRNA-133a-3p remarkably increased in MIF-Exo. The biological effects of HUVECs and H9C2 cardiomyocytes were attenuated with incubation of MIF-Exo and miR-133a-3p inhibitors. And these effects were accentuated with incubation of siMIF-Exo and miR-133a-3p mimics, followed by p-AKT protein level up-regulated.
Conclusion MIF-Exo enhance the effects on promoting angiogenesis, inhibiting apoptosis, reducing fibrosis and preserving heart function, in vitro and in vivo. The miR-133a-3p and its downstream AKT signal pathway were involved in these biological activities of MIF-Exo.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
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