Expression of WAVEs, the WASP (Wiskott-Aldrich syndrome protein) family of verprolin homologous proteins, in human wound tissues and the cellular impact of WAVEs on keratinocytes [Abstract]

Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111, Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409, Patel, Girish Khandubhai and Harding, Keith Gordon 2010. Expression of WAVEs, the WASP (Wiskott-Aldrich syndrome protein) family of verprolin homologous proteins, in human wound tissues and the cellular impact of WAVEs on keratinocytes [Abstract]. Wound Repair and Regeneration 18 (6) , A84. 10.1111/j.1524-475X.2010.00633.x

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Abstract

Wiskott-Aldrich syndrome (WAS) WAS protein family verprolin homologous proteins, WAVEs, are a group of proteins that regulate actin polymerisation. In the present study, we investigated the pattern of expression of the WAVE family members, WAVE-1/2/3, in a cohort of human wound tissues together with normal skins and evaluated the role of these molecules in the migration of keratinocytes. Quantitative analysis of WAVE transcript demonstrated that there was a significant reduction of the WAVE-3 transcripts in chronic wound tissues, compared with normal skin and acute wound tissue (p=0.002). Marginal reduction of the WAVE-1 and WAVE-2 transcripts in chronic wounds were also seen (p=0.057 and p=0.054, respectively). Immunohistochemnical analysis confirmed the changes as seen with the transcripts. Using an electric cell impedance sensing (ECIS), we created in vitro cell models using keratinocytes in which we knockdown the expression of WAVE-1 and WAVE-3. It was shown that knocking down WAVE-3 had a significant effect on the migration and reepithelialisation of keratinocytes and that manipulation of WAVE-1 only had marginal effect. We further demonstrated that the impact of WAVE on cell migration is independent upon the PLCg and ERK pathway, but in the downstream requires PI3K pathway and ROCK pathways. In conclusion, WAVE-3 is essential to the re-epithelialisation of keratinocytes. Aberrant expression of WAVEs is linked to the healing process of clinical wounds and loss of WAVE-3 is a particular indicator of an abnormally healing wound. The WAVE proteins have a significant predicative and therapeutic value in wound healing.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine European Cancer Stem Cell Research Institute (ECSCRI)
Subjects:	R Medicine > R Medicine (General)
Additional Information:	20th Meeting of the European Tissue Repair Society Gent, Belgium September 15–17, 2010 Basic and Clinical Research: Building Blocks in the Puzzle of Tissue Repair
Publisher:	Wiley-Blackwell
ISSN:	1067-1927
Last Modified:	22 Jun 2023 10:01
URI:	https://orca.cardiff.ac.uk/id/eprint/18948

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