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Hong Gao
Shanghai Sixth Peoples Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9347-3293
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Background: Diabetic wounds are a disturbing and rapidly growing clinical problem. A novel peptide, parathyroid hormone related peptide (PTHrP-2), is assumed as multifunctional factor in angiogenesis, fibrogenesis and re-epithelization. This study aims to test PTHrP-2 efficiency and mechanism in wound healing. Methods: Through repair phenomenon in vivo some problems were detected, and further research on their mechanisms was made. In vivo therapeutic effects of PTHrP-2 were determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 were determined by proliferation, migration, Vascular Endothelial Grown Factor and collagen I secretion of cells and Akt/ Erk1/2 pathway change. In vitro indirect effects of PTHrP-2 was study via exosomes. Exosomes from PTHrP-2 untreated and treated HUVECs and HFF-1 cells were insolated and identified. Exosomes were co-cultured with original cells, HUVECs or HFF-1 cells, and epithelial cells. Proliferation and migration and pathway change were observed. PTHrP-2-HUVEC-Exos were added into in vivo wound to testify its hub role in PTHrP-2 indirect effects in wound healing. Results: In vivo, PTHrP-2 exerted multifunctional pro-angiogenesis, pro-firbogenesis and re-epithelization effects. In vitro, PTHrP-2 promoted proliferation and migration of endothelial and fibroblast cells, but had no effect on epithelial cells. Therefore, we tested PTHrP-2 indirect effects via exosomes. PTHrP-2 intensified intercellular communication between endothelial cells and fibroblasts and initiated endothelial-epithelial intercellular communication. PTHrP-2-HUVEC-Exos played a hub role in PTHrP-2 indirect effects in wound healing. Conclusion: These findings of this study indicated that PTHrP-2, a multifunctional factor, could promote wound healing via synergistic multicellular stimulating and exosomal activities. Key words PTH, multifunctional factor, diabetic wound, exosomes, synergistic effect
Keywords
PTH, multifunctional factor, diabetic wound, exosomes, synergistic effect
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View the published article at Cell Communication and Signaling.
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Received 26 Feb, 2020
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On 22 Feb, 2020
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On 21 Feb, 2020
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On 18 Feb, 2020
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Received 15 Feb, 2020
Reviewer #1 agreed
On 07 Feb, 2020
Reviewers invited
Invitations sent on 05 Feb, 2020
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On 04 Feb, 2020
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Editor invited
On 03 Feb, 2020
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Editorial decision: Major Revision
On 02 Feb, 2020
Review #1 received
Received 19 Dec, 2019
Reviewers invited
Invitations sent on 06 Dec, 2019
Reviewer #1 agreed
On 06 Dec, 2019
Editor assigned
On 04 Dec, 2019
First submitted
On 03 Dec, 2019
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A new preprint design is coming!
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See the published version of this preprint at Cell Communication and Signaling.
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
Hong Gao
Shanghai Sixth Peoples Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9347-3293
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 Cell Communication and Signaling.
Version 3
Posted 21 Feb, 2020
No community comments so far
Review #1 received
Received 26 Feb, 2020
Editorial decision: Accept
On 26 Feb, 2020
Reviewer #1 agreed
On 22 Feb, 2020
Reviewers invited
Invitations sent on 21 Feb, 2020
Editor assigned
On 21 Feb, 2020
Submission checks complete
On 20 Feb, 2020
Editor invited
On 20 Feb, 2020
No comments provided
Editorial decision: Minor Revision
On 18 Feb, 2020
Review #1 received
Received 15 Feb, 2020
Reviewer #1 agreed
On 07 Feb, 2020
Reviewers invited
Invitations sent on 05 Feb, 2020
Editor assigned
On 04 Feb, 2020
Submission checks complete
On 03 Feb, 2020
Editor invited
On 03 Feb, 2020
No comments provided
Editorial decision: Major Revision
On 02 Feb, 2020
Review #1 received
Received 19 Dec, 2019
Reviewers invited
Invitations sent on 06 Dec, 2019
Reviewer #1 agreed
On 06 Dec, 2019
Editor assigned
On 04 Dec, 2019
First submitted
On 03 Dec, 2019
Submission checks complete
On 03 Dec, 2019
Editor invited
On 03 Dec, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cell Communication and Signaling
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Cell Communication and Signaling.
Background: Diabetic wounds are a disturbing and rapidly growing clinical problem. A novel peptide, parathyroid hormone related peptide (PTHrP-2), is assumed as multifunctional factor in angiogenesis, fibrogenesis and re-epithelization. This study aims to test PTHrP-2 efficiency and mechanism in wound healing. Methods: Through repair phenomenon in vivo some problems were detected, and further research on their mechanisms was made. In vivo therapeutic effects of PTHrP-2 were determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 were determined by proliferation, migration, Vascular Endothelial Grown Factor and collagen I secretion of cells and Akt/ Erk1/2 pathway change. In vitro indirect effects of PTHrP-2 was study via exosomes. Exosomes from PTHrP-2 untreated and treated HUVECs and HFF-1 cells were insolated and identified. Exosomes were co-cultured with original cells, HUVECs or HFF-1 cells, and epithelial cells. Proliferation and migration and pathway change were observed. PTHrP-2-HUVEC-Exos were added into in vivo wound to testify its hub role in PTHrP-2 indirect effects in wound healing. Results: In vivo, PTHrP-2 exerted multifunctional pro-angiogenesis, pro-firbogenesis and re-epithelization effects. In vitro, PTHrP-2 promoted proliferation and migration of endothelial and fibroblast cells, but had no effect on epithelial cells. Therefore, we tested PTHrP-2 indirect effects via exosomes. PTHrP-2 intensified intercellular communication between endothelial cells and fibroblasts and initiated endothelial-epithelial intercellular communication. PTHrP-2-HUVEC-Exos played a hub role in PTHrP-2 indirect effects in wound healing. Conclusion: These findings of this study indicated that PTHrP-2, a multifunctional factor, could promote wound healing via synergistic multicellular stimulating and exosomal activities. Key words PTH, multifunctional factor, diabetic wound, exosomes, synergistic effect
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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