nWASP Inhibition Increases Wound Healing via TrKb/PLCγ Signalling

Frugtniet, Bethan A, Ruge, Fiona, Sanders, Andrew J ORCID: 0000-0002-7997-5286, Owen, Sioned, Harding, Keith G, Jiang, Wen G and Martin, Tracey A (2023) nWASP Inhibition Increases Wound Healing via TrKb/PLCγ Signalling. Biomolecules, 13 (2). ART 379. doi:10.3390/biom13020379

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Abstract

Background: Chronic wounds represent a major burden to patients and healthcare systems and identifying new therapeutic targets to encourage wound healing is a significant challenge. This study evaluated nWASP as a new therapeutic target in human wound healing and determined how this can be regulated. (2) Methods: Clinical cohorts from patients with chronic wounds were tested for the expression of nWASP and cell models were employed to evaluate the influence of nWASP on cellular functions that are key to the healing process following knockdown and/or the use of nWASP-specific inhibitors. (3) Results: nWASP was significantly elevated at transcript levels in human non-healing chronic wounds versus healing tissues. nWASP inhibitors, wiskostatin and 187-1, along with the knockdown of nWASP, modified both HaCaT and HECV cell behaviour. We then identified two signalling pathways affected by nWASP inhibition: TrkB signalling and downstream PLCγ1 phosphorylation were impaired by nWASP inhibition in HaCaT cells. The healing of wounds in a diabetic murine model was significantly improved with an nWASP inhibitor treatment. (4) Conclusions: This study showed that nWASP activity was related to the non-healing behaviour of chronic wounds and together with the findings in the in vivo models, it strongly suggested nWASP as a therapeutic target in non-healing wounds that are regulated via TrkB and PLCγ1 signalling.

Item Type:	Article
Article Type:	Article
Uncontrolled Keywords:	Wound healing; nWASP; Therapy; Chronic wounds; Motility
Subjects:	Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology
Divisions:	Schools and Research Institutes > School of Education and Science
Research Priority Areas:	Place, Environment and Community
Depositing User:	Anna Kerr
Date Deposited:	02 Mar 2023 10:41
Last Modified:	31 Aug 2023 08:57
URI:	https://eprints.glos.ac.uk/id/eprint/12429

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