The Connexin Mimetic Peptide Gap27 and Cx43-Knockdown Reveal Differential Roles for Connexin43 in Wound Closure Events in Skin Model Systems

International Journal of Molecular Sciences
Chrysovalantou FanikuPatricia E M Martin

Abstract

In the epidermis, remodelling of Connexin43 is a key event in wound closure. However, controversy between the role of connexin channel and non-channel functions exist. We compared the impact of SiRNA targeted to Connexin43 and the connexin mimetic peptide Gap27 on scrape wound closure rates and hemichannel signalling in adult keratinocytes (AK) and fibroblasts sourced from juvenile foreskin (JFF), human neonatal fibroblasts (HNDF) and adult dermal tissue (ADF). The impact of these agents, following 24 h exposure, on GJA1 (encoding Connexin43), Ki67 and TGF-β1 gene expression, and Connexin43 and pSmad3 protein expression levels, were examined by qPCR and Western Blot respectively. In all cell types Gap27 (100-100 μM) attenuated hemichannel activity. In AK and JFF cells, Gap27 (100 nM-100 μM) enhanced scrape wound closure rates by ~50% but did not influence movement in HNDF or ADF cells. In both JF and AK cells, exposure to Gap27 for 24 h reduced the level of Cx43 protein expression but did not affect the level in ADF and HNDF cells. Connexin43-SiRNA enhanced scrape wound closure in all the cell types under investigation. In HDNF and ADF, Connexin43-SiRNA enhanced cell proliferation rates, with enhanced proliferation also observe...Continue Reading

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Citations

Feb 3, 2019·Journal of Cellular Physiology·Laura García-VegaPatricia E Martin
Jun 28, 2020·Journal of Cellular Physiology·Louise NugentCatherine S Wright
Jun 30, 2018·International Journal of Molecular Sciences·Myo HtetYvonne Dempsie
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May 13, 2018·International Journal of Molecular Sciences·Marc ChansonPatricia E Martin
Jun 20, 2018·International Journal of Molecular Sciences·Jade MontgomeryRobert G Gourdie
Jan 29, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Li WanYuval Rinkevich
Jan 21, 2021·Biology·Laura Garcia-VegaPatricia E Martin
Jun 3, 2021·Journal of Cardiovascular Development and Disease·Spencer R MarshRobert G Gourdie
Jul 3, 2021·International Journal of Molecular Sciences·Erin M O'ShaughnessyPatricia E Martin
Aug 8, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Mauricio A RetamalJimmy Stehberg
Nov 5, 2021·BMC Anesthesiology·Dongdong YuanDezhao Liu

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Methods Mentioned

BETA
biopsies
antisense oligonucleotides
gene array
transfection
scraping
PCR
electrophoresis

Software Mentioned

Image J
Odyssey
Primerdesign
GraphPad Prism
Excel
AQMsoftware

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