Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/127212
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Type: | Journal article |
Title: | Attenuation of flightless I increases human pericyte proliferation, migration and angiogenic functions and improves healing in murine diabetic wounds |
Author: | Thomas, H.M. Ahangar, P. Hofma, B.R. Strudwick, X.L. Fitridge, R. Mills, S.J. Cowin, A.J. |
Citation: | International Journal of Molecular Sciences, 2020; 21(16):1-15 |
Publisher: | MDPI AG |
Issue Date: | 2020 |
ISSN: | 1422-0067 1422-0067 |
Statement of Responsibility: | Hannah M Thomas, Parinaz Ahangar, Benjamin R Hofma, Xanthe L Strudwick, Robert Fitridge, Stuart J Mills and Allison J Cowin |
Abstract: | Pericytes are peri-vascular mural cells which have an important role in the homeostatic regulation of inflammatory and angiogenic processes. Flightless I (Flii) is a cytoskeletal protein involved in regulating cellular functions, but its involvement in pericyte activities during wound healing is unknown. Exacerbated inflammation and reduced angiogenesis are hallmarks of impaired diabetic healing responses, and strategies aimed at regulating these processes are vital for improving healing outcomes. To determine the effect of altering Flii expression on pericyte function, in vitro and in vivo studies were performed to assess the effect on healing, inflammation and angiogenesis in diabetic wounds. Here, we demonstrated that human diabetic wounds display upregulated expression of the Flii protein in conjunction with a depletion in the number of platelet derived growth factor receptor β (PDGFRβ) +/ neural glial antigen 2 (NG2) + pericytes present in the dermis. Human pericytes were found to be positive for Flii and attenuating its expression in vitro through siRNA knockdown led to enhanced proliferation, migration and angiogenic functions. Genetic knockdown of Flii in a streptozotocin-induced murine model of diabetes led to increased numbers of pericytes within the wound. This was associated with dampened inflammation, an increased rate of angiogenic repair and improved wound healing. Our findings show that Flii expression directly impacts pericyte functions, including proliferation, motility and angiogenic responses. This suggests that Flii regulation of pericyte function may be in part responsible for the changes in pericyte-related processes observed in diabetic wounds. |
Keywords: | angiogenesis diabetes flightless I inflammation pericytes wound healing |
Rights: | © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
DOI: | 10.3390/ijms21165599 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1002009 |
Published version: | http://dx.doi.org/10.3390/ijms21165599 |
Appears in Collections: | Aurora harvest 4 Chemistry and Physics publications |
Files in This Item:
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hdl_127212.pdf | Published version | 3.28 MB | Adobe PDF | View/Open |
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