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Research
Weishuai Lian
Shanghai Tenth People's Hospital
Corresponding Author
Haijun Zhang
Shanghai Tenth People's Hospital
Corresponding Author
Xiaoping Zhang
Shanghai Tenth People's Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1592-2353
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Diabetes is associated with the dysfunction of endothelial progenitor cells (EPCs), characterized as impaired angiogenesis, a phenomenon thought to be involved in the development of diabetic foot. LncRNA plays an essential role in microvascular dysfunction and signaling pathways in patients with diabetes. LncRNA taurine upregulated gene 1 (TUG1) participates in angiogenesis in various cells. However, the mechanisms of TUG1 activity in EPCs have not been elucidated.
Methods
We isolated and then characterized EPCs from the peripheral blood of mice using immunofluorescence and flow cytometry. Western blot detected the wnt/β-catenin pathway in high glucose treated EPCs. Bioinformatics analysis predicted a putative binding site for TUG1 on miR-29c-3p. The interactions among TUG1, platelet-derived growth factor-BB (PDGF-BB) and miR-29c-3p were analyzed by luciferase assays. In vivo, diabetic mouse ischemic limb were treated with normal saline or TUG1 overexpression lentiviruses.
Results
We found that EPC migration, invasion and tube formation declined after treatment with high glucose, but improved with TUG1 overexpression. Mechanically, wnt/β-catenin pathway and autophagy were involved in the function of TUG1 overexpression in high glucose treated EPCs. Moreover, TUG1 regulates the PDGF-BB/wnt pathway and function of high glucose treated EPCs via miR-29c-3p. In vivo, injection of TUG1 lentivirus in a diabetic mouse ischemic limb model stimulated angiogenesis.
Conclusions
Our findings suggest that TUG1 restores high glucose treated EPC function by regulating miR-29c-3p/PDGF-BB/Wnt signaling.
Keywords
LncRNA taurine upregulated gene 1, Platelet-derived growth factor-BB, Endothelial progenitor cells, Diabetes, Angiogenesis
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CURRENT STATUS: Published
View the published article at Stem Cell Research & Therapy.
No community comments so far
Review #2 received
Received 03 Aug, 2020
Review #1 received
Received 03 Aug, 2020
Editorial decision: Accept
On 03 Aug, 2020
Reviewer #2 agreed
On 02 Aug, 2020
Reviewer #1 agreed
On 01 Aug, 2020
Reviewers invited
Invitations sent on 31 Jul, 2020
Editor assigned
On 29 Jul, 2020
Submission checks complete
On 28 Jul, 2020
Editor invited
On 28 Jul, 2020
No comments provided
Editorial decision: Major Revision
On 19 Jul, 2020
Review #2 received
Received 16 Jul, 2020
Review #1 received
Received 13 Jul, 2020
Reviewer #2 agreed
On 12 Jul, 2020
Reviewers invited
Invitations sent on 10 Jul, 2020
Reviewer #1 agreed
On 10 Jul, 2020
Editor assigned
On 08 Jul, 2020
Submission checks complete
On 07 Jul, 2020
Editor invited
On 07 Jul, 2020
Version 1
Posted 05 Jun, 2020
No comments provided
Review #1 received
Received 17 Jun, 2020
Editorial decision: Major Revision
On 17 Jun, 2020
Review #2 received
Received 16 Jun, 2020
Reviewer #4 agreed
On 12 Jun, 2020
Reviewer #3 agreed
On 11 Jun, 2020
Editor assigned
On 10 Jun, 2020
Reviewers invited
Invitations sent on 10 Jun, 2020
Reviewer #1 agreed
On 10 Jun, 2020
Reviewer #2 agreed
On 10 Jun, 2020
Editor invited
On 09 Jun, 2020
Submission checks complete
On 03 Jun, 2020
First submitted
On 02 Jun, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at Stem Cell Research & Therapy.
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
Weishuai Lian
Shanghai Tenth People's Hospital
Corresponding Author
Haijun Zhang
Shanghai Tenth People's Hospital
Corresponding Author
Xiaoping Zhang
Shanghai Tenth People's Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1592-2353
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 Stem Cell Research & Therapy.
No community comments so far
Review #2 received
Received 03 Aug, 2020
Review #1 received
Received 03 Aug, 2020
Editorial decision: Accept
On 03 Aug, 2020
Reviewer #2 agreed
On 02 Aug, 2020
Reviewer #1 agreed
On 01 Aug, 2020
Reviewers invited
Invitations sent on 31 Jul, 2020
Editor assigned
On 29 Jul, 2020
Submission checks complete
On 28 Jul, 2020
Editor invited
On 28 Jul, 2020
No comments provided
Editorial decision: Major Revision
On 19 Jul, 2020
Review #2 received
Received 16 Jul, 2020
Review #1 received
Received 13 Jul, 2020
Reviewer #2 agreed
On 12 Jul, 2020
Reviewers invited
Invitations sent on 10 Jul, 2020
Reviewer #1 agreed
On 10 Jul, 2020
Editor assigned
On 08 Jul, 2020
Submission checks complete
On 07 Jul, 2020
Editor invited
On 07 Jul, 2020
Version 1
Posted 05 Jun, 2020
No comments provided
Review #1 received
Received 17 Jun, 2020
Editorial decision: Major Revision
On 17 Jun, 2020
Review #2 received
Received 16 Jun, 2020
Reviewer #4 agreed
On 12 Jun, 2020
Reviewer #3 agreed
On 11 Jun, 2020
Editor assigned
On 10 Jun, 2020
Reviewers invited
Invitations sent on 10 Jun, 2020
Reviewer #1 agreed
On 10 Jun, 2020
Reviewer #2 agreed
On 10 Jun, 2020
Editor invited
On 09 Jun, 2020
Submission checks complete
On 03 Jun, 2020
First submitted
On 02 Jun, 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 Stem Cell Research & Therapy.
Background
Diabetes is associated with the dysfunction of endothelial progenitor cells (EPCs), characterized as impaired angiogenesis, a phenomenon thought to be involved in the development of diabetic foot. LncRNA plays an essential role in microvascular dysfunction and signaling pathways in patients with diabetes. LncRNA taurine upregulated gene 1 (TUG1) participates in angiogenesis in various cells. However, the mechanisms of TUG1 activity in EPCs have not been elucidated.
Methods
We isolated and then characterized EPCs from the peripheral blood of mice using immunofluorescence and flow cytometry. Western blot detected the wnt/β-catenin pathway in high glucose treated EPCs. Bioinformatics analysis predicted a putative binding site for TUG1 on miR-29c-3p. The interactions among TUG1, platelet-derived growth factor-BB (PDGF-BB) and miR-29c-3p were analyzed by luciferase assays. In vivo, diabetic mouse ischemic limb were treated with normal saline or TUG1 overexpression lentiviruses.
Results
We found that EPC migration, invasion and tube formation declined after treatment with high glucose, but improved with TUG1 overexpression. Mechanically, wnt/β-catenin pathway and autophagy were involved in the function of TUG1 overexpression in high glucose treated EPCs. Moreover, TUG1 regulates the PDGF-BB/wnt pathway and function of high glucose treated EPCs via miR-29c-3p. In vivo, injection of TUG1 lentivirus in a diabetic mouse ischemic limb model stimulated angiogenesis.
Conclusions
Our findings suggest that TUG1 restores high glucose treated EPC function by regulating miR-29c-3p/PDGF-BB/Wnt signaling.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
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