dc.contributor.author | Huang, Y | |
dc.contributor.author | Jedlickova, H | |
dc.contributor.author | Cai, Y | |
dc.contributor.author | Rehman, A | |
dc.contributor.author | Gammon, L | |
dc.contributor.author | Ahmad, US | |
dc.contributor.author | Uttagomol, J | |
dc.contributor.author | Chance, R | |
dc.contributor.author | Kang, A | |
dc.contributor.author | Parkinson, EK | |
dc.contributor.author | Fortune, F | |
dc.contributor.author | Wan, H | |
dc.date.accessioned | 2024-07-31T14:35:27Z | |
dc.date.available | 2024-07-31T14:35:27Z | |
dc.date.issued | 2022-04-19 | |
dc.identifier.citation | Huang Y, Jedlicˇ kova´ H, Cai Y, Rehman A, Gammon L, Ahmad US, Uttagomol J, Parkinson EK, Fortune F and Wan H (2021) Oxidative StressMediated YAP Dysregulation Contributes to the Pathogenesis of Pemphigus Vulgaris. Front. Immunol. 12:649502. doi: 10.3389/fimmu.2021.649502 | en_US |
dc.identifier.issn | 0007-0963 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/98524 | |
dc.description.abstract | Pemphigus Vulgaris (PV) is a life-threatening autoimmune disease manifested with blisters in the skin and mucosa and caused by autoantibodies against adhesion protein desmoglein-3 (Dsg3) expressed in epithelial membrane linings of these tissues. Despite many studies, the pathogenesis of PV remains incompletely understood. Recently we have shown Dsg3 plays a role in regulating the yes-associated protein (YAP), a co-transcription factor and mechanical sensor, and constraining reactive oxygen species (ROS). This study investigated the effect of PV sera as well as the anti-Dsg3 antibody AK23 on these molecules. We detected elevated YAP steady-state protein levels in PV cells surrounding blisters and perilesional regions and in keratinocytes treated with PV sera and AK23 with concomitant transient ROS overproduction. Cells treated with hydrogen peroxide also exhibited augmented nuclear YAP accompanied by reduction of Dsg3 and α-catenin, a negative regulator of YAP. As expected, transfection of α-catenin-GFP plasmid rendered YAP export from the nucleus evoked by hydrogen peroxide. In addition, suppression of total YAP was observed in hydrogen peroxide treated cells exposed to antioxidants with enhanced cell-cell adhesion being confirmed by decreased fragmentation in the dispase assay compared to hydrogen peroxide treatment alone. On the other hand, the expression of exogenous YAP disrupted intercellular junction assembly. In contrast, YAP depletion resulted in an inverse effect with augmented expression of junction assembly proteins, including Dsg3 and α-catenin capable of abolishing the effect of AK23 on Dsg3 expression. Finally, inhibition of other kinase pathways, including p38MAPK, also demonstrated suppression of YAP induced by hydrogen peroxide. Furthermore, antioxidant treatment of keratinocytes suppressed PV sera-induced total YAP accumulation. In conclusion, this study suggests that oxidative stress coupled with YAP dysregulation attributes to PV blistering, implying antioxidants may be beneficial in the treatment of PV. | en_US |
dc.format.extent | E43 - E44 | |
dc.publisher | Frontiers Media | en_US |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | |
dc.title | Oxidative stress-mediated yes-associated protein dysregulation contributes to the pathogenesis of pemphigus vulgaris | en_US |
dc.type | Conference Proceeding | en_US |
dc.rights.holder | © 2021 Huang, Jedličkova, Cai, Rehman, Gammon, Ahmad, Uttagomol, ́ Parkinson, Fortune and Wan | |
pubs.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000820115600142&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 187 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
qmul.funder | Dissecting the role of YAP in the pathogenesis of Pemphigus Vulgaris, an autoimmune blistering disease::Barts Charity | en_US |
rioxxterms.funder.project | b215eee3-195d-4c4f-a85d-169a4331c138 | en_US |