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PTH Derivative promotes wound healing via synergistic multicellular stimulating and exosomal activities
- Source :
- Cell Communication and Signaling, Vol 18, Iss 1, Pp 1-15 (2020)
- Publication Year :
- 2020
- Publisher :
- BMC, 2020.
-
Abstract
- Abstract 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. Graphical abstract
Details
- Language :
- English
- ISSN :
- 1478811X
- Volume :
- 18
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Communication and Signaling
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.8465a521918c4eafac2f372a75fec413
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s12964-020-00541-w