{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T16:00:18Z","timestamp":1776096018328,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"24","funder":[{"name":"Chongqing Basic Science and Frontier Technology Research Project","award":["cstc2017jcyjAX0479"],"award-info":[{"award-number":["cstc2017jcyjAX0479"]}]},{"name":"National Natural Science Foundation of China Youth Science Fund Project","award":["81703127"],"award-info":[{"award-number":["81703127"]}]},{"name":"Chongqing Science and Health Joint Medical Research Project General Project","award":["2024MSXM069"],"award-info":[{"award-number":["2024MSXM069"]}]},{"name":"Chongqing Natural Science Foundation General Project","award":["2023NSCQ-MSX0372"],"award-info":[{"award-number":["2023NSCQ-MSX0372"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pemphigus vulgaris (PV) is an autoimmune skin disorder characterized by the loss of cell cohesion, with the histone deacetylase 1 (HDAC1) and lysine demethylase 1A (KDM1A) playing critical roles in its pathogenesis. This study aimed to elucidate the molecular mechanisms behind PV, focusing on the function of HDAC1 and KDM1A in disease onset and progression. Based on in vitro and in vivo PV models, we observed a significant increase in HDAC1 mRNA and protein levels in skin tissues of PV patients. Inhibition of HDAC1 ameliorated cell damage and reduced the loss of cell cohesion in human epidermal keratinocytes (HEKs) induced by PV-IgG. Our findings suggest that HDAC1 regulates KDM1A expression through deacetylation, with a notable deficiency in KDM1A expression in PV. Overexpression of KDM1A mitigated cell damage and cohesion loss. The extracellular signal-regulated kinase (ERK) pathway serves as a downstream executor of the HDAC1\/KDM1A axis. Inhibiting HDAC1 and increasing KDM1A expression suppressed ERK phosphorylation, reducing PV-related apoptosis. These insights provide a new perspective on treating PV, highlighting the therapeutic potential of targeting HDAC1 expression. The regulatory mechanism of the HDAC1\/KDM1A\/ERK axis offers crucial clues for understanding PV pathogenesis and developing novel treatments.<\/jats:p>","DOI":"10.1093\/hmg\/ddae090","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T19:32:18Z","timestamp":1730230338000},"page":"2133-2144","source":"Crossref","is-referenced-by-count":2,"title":["HDAC1-mediated regulation of KDM1A in pemphigus vulgaris: unlocking mechanisms on ERK pathway activation and cohesion loss"],"prefix":"10.1093","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0184-3001","authenticated-orcid":false,"given":"Mao","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University , No. 1 Youyi Road, Yuzhong District, Chongqing 400016 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6643-3835","authenticated-orcid":false,"given":"Ziqi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University , No. 1 Youyi Road, Yuzhong District, Chongqing 400016 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1014-6596","authenticated-orcid":false,"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University , No. 1 Youyi Road, Yuzhong District, Chongqing 400016 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4401-9022","authenticated-orcid":false,"given":"Yangmei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University , No. 1 Youyi Road, Yuzhong District, Chongqing 400016 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6198-2861","authenticated-orcid":false,"given":"Aijun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University , No. 1 Youyi Road, Yuzhong District, Chongqing 400016 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2410-5101","authenticated-orcid":false,"given":"Bin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University , No. 1 Youyi Road, Yuzhong District, Chongqing 400016 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"2024121021335928000_ref1","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.3390\/medicina57101080","article-title":"An updated review of pemphigus diseases","volume":"57","author":"Malik","year":"2021","journal-title":"Medicina (Kaunas)"},{"key":"2024121021335928000_ref2","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/S0140-6736(19)31778-7","article-title":"Pemphigus","volume":"394","author":"Schmidt","year":"2019","journal-title":"Lancet"},{"key":"2024121021335928000_ref3","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1186\/s12917-020-02677-w","article-title":"Deep pemphigus (pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus) in dogs, cats and horses: a comprehensive review","volume":"16","author":"Tham","year":"2020","journal-title":"BMC Vet Res"},{"key":"2024121021335928000_ref4","doi-asserted-by":"crossref","first-page":"17026","DOI":"10.1038\/nrdp.2017.26","article-title":"Pemphigus","volume":"3","author":"Kasperkiewicz","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2024121021335928000_ref5","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.jaad.2010.06.033","article-title":"Rituximab used as a first-line single agent in the treatment of pemphigus vulgaris","volume":"65","author":"Craythorne","year":"2011","journal-title":"J Am Acad Dermatol"},{"key":"2024121021335928000_ref6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.aanat.2018.11.006","article-title":"Desmogleins as signaling hubs regulating cell cohesion and tissue\/organ function in skin and heart - EFEM lecture 2018","volume":"226","author":"Waschke","year":"2019","journal-title":"Ann Anat"},{"key":"2024121021335928000_ref7","doi-asserted-by":"crossref","first-page":"a015297","DOI":"10.1101\/cshperspect.a015297","article-title":"Desmosomes: regulators of cellular signaling and adhesion in epidermal health and disease","volume":"4","author":"Johnson","year":"2014","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2024121021335928000_ref8","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jid.2017.06.022","article-title":"Mechanisms causing loss of keratinocyte cohesion in pemphigus","volume":"138","author":"Spindler","year":"2018","journal-title":"J Invest Dermatol"},{"key":"2024121021335928000_ref9","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.det.2011.03.020","article-title":"The genetics of pemphigus","volume":"29","author":"Sinha","year":"2011","journal-title":"Dermatol Clin"},{"key":"2024121021335928000_ref10","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.3390\/ijms21062178","article-title":"Paraneoplastic dermatoses: a brief general review and an extensive analysis of paraneoplastic pemphigus and paraneoplastic Dermatomyositis","volume":"21","author":"Didona","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2024121021335928000_ref11","first-page":"535","article-title":"Environmental triggers and epigenetic deregulation in autoimmune disease","volume":"12","author":"Javierre","year":"2011","journal-title":"Discov Med"},{"key":"2024121021335928000_ref12","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1021\/acschembio.6b00776","article-title":"LSD1 substrate binding and gene expression are affected by HDAC1-mediated deacetylation","volume":"12","author":"Nalawansha","year":"2017","journal-title":"ACS Chem Biol"},{"key":"2024121021335928000_ref13","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1093\/cvr\/cvab198","article-title":"HDAC1: an environmental sensor regulating endothelial function","volume":"118","author":"Dunaway","year":"2022","journal-title":"Cardiovasc Res"},{"key":"2024121021335928000_ref14","article-title":"Regulating the regulators: the role of histone deacetylase 1 (HDAC1) in erythropoiesis","volume":"21","author":"Kim","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2024121021335928000_ref15","doi-asserted-by":"crossref","first-page":"3579","DOI":"10.1038\/s41598-017-03697-7","article-title":"Different signaling patterns contribute to loss of keratinocyte cohesion dependent on autoantibody profile in pemphigus","volume":"7","author":"Walter","year":"2017","journal-title":"Sci Rep"},{"key":"2024121021335928000_ref16","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1002\/jcp.27265","article-title":"HDAC1\/2-mediated regulation of JNK and ERK phosphorylation in bovine mammary epithelial cells in response to TNF-alpha","volume":"234","author":"Romanick","year":"2019","journal-title":"J Cell Physiol"},{"key":"2024121021335928000_ref17","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.3389\/fimmu.2019.02883","article-title":"Role of PKC and ERK Signaling in epidermal blistering and desmosome regulation in pemphigus","volume":"10","author":"Egu","year":"2019","journal-title":"Front Immunol"},{"key":"2024121021335928000_ref18","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1346-8138.2009.00797.x","article-title":"Immune dysregulation of pemphigus in humans and mice","volume":"37","author":"Yokoyama","year":"2010","journal-title":"J Dermatol"},{"key":"2024121021335928000_ref19","doi-asserted-by":"crossref","first-page":"884067","DOI":"10.3389\/fimmu.2022.884067","article-title":"Mechanisms causing acantholysis in pemphigus-lessons from human skin","volume":"13","author":"Egu","year":"2022","journal-title":"Front Immunol"},{"key":"2024121021335928000_ref20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12016-017-8662-z","article-title":"Pemphigus: a comprehensive review on pathogenesis, clinical presentation and novel therapeutic approaches","volume":"54","author":"Pollmann","year":"2018","journal-title":"Clin Rev Allergy Immunol"},{"key":"2024121021335928000_ref21","doi-asserted-by":"crossref","first-page":"104284","DOI":"10.1016\/j.cellimm.2021.104284","article-title":"HDAC1 potentiates CD4 + T cell activation by inhibiting miR-124 and promoting IRF1 in systemic lupus erythematosus","volume":"362","author":"Chen","year":"2021","journal-title":"Cell Immunol"},{"key":"2024121021335928000_ref22","doi-asserted-by":"crossref","first-page":"970","DOI":"10.55563\/clinexprheumatol\/1xsigp","article-title":"Histone deacetylase 1 is increased in rheumatoid arthritis synovium and promotes synovial cell hyperplasia and synovial inflammation in the collagen-induced arthritis mouse model via the microRNA-124-dependent MARCKS-JAK\/STAT axis","volume":"39","author":"Meng","year":"2021","journal-title":"Clin Exp Rheumatol"},{"key":"2024121021335928000_ref23","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.reuma.2022.12.008","article-title":"Evaluation of epigenetic-related gene expression (DNMT, HDAC1) in Iranian patients with systemic lupus erythematosus","volume":"19","author":"Abbasifard","year":"2023","journal-title":"Reumatol Clin (Engl Ed)"},{"key":"2024121021335928000_ref24","doi-asserted-by":"crossref","first-page":"6359652","DOI":"10.1155\/2021\/6359652","article-title":"Ellagic acid alleviates rheumatoid arthritis in rats through inhibiting MTA1\/HDAC1-mediated Nur77 deacetylation","volume":"2021","author":"Song","year":"2021","journal-title":"Mediat Inflamm"},{"key":"2024121021335928000_ref25","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1080\/13880209.2021.1941131","article-title":"Wutou decoction attenuates rheumatoid arthritis by modulating the Ahr\/LOC101928120\/SHC1 pathway","volume":"59","author":"Wu","year":"2021","journal-title":"Pharm Biol"},{"key":"2024121021335928000_ref26","first-page":"157","article-title":"Histone deacetylase 1 and Sirtuin 1 expression in psoriatic skin: a comparison between guttate and plaque psoriasis","volume":"10","author":"Hwang","year":"2020","journal-title":"Life (Basel)"},{"key":"2024121021335928000_ref27","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/bs.acr.2018.02.006","article-title":"Advances and challenges of HDAC inhibitors in cancer therapeutics","volume":"138","author":"McClure","year":"2018","journal-title":"Adv Cancer Res"},{"key":"2024121021335928000_ref28","doi-asserted-by":"crossref","first-page":"12460","DOI":"10.1021\/acs.jmedchem.0c00830","article-title":"Thirty years of HDAC inhibitors: 2020 insight and hindsight","volume":"63","author":"Ho","year":"2020","journal-title":"J Med Chem"},{"key":"2024121021335928000_ref29","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.jid.2019.07.691","article-title":"First glimpse of epigenetic effects on pemphigus Foliaceus","volume":"140","author":"Spadoni","year":"2020","journal-title":"J Invest Dermatol"},{"key":"2024121021335928000_ref30","first-page":"217","article-title":"Construction and evaluation of short hairpin RNAs for knockdown of Metadherin mRNA","volume":"13","author":"Zare","year":"2021","journal-title":"Avicenna J Med Biotechnol"},{"key":"2024121021335928000_ref31","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3389\/fimmu.2018.00370","article-title":"Soluble Fas ligand is essential for blister formation in pemphigus","volume":"9","author":"Lotti","year":"2018","journal-title":"Front Immunol"},{"key":"2024121021335928000_ref32","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S0076-6879(04)92023-X","article-title":"Adeno-associated virus vectors for short hairpin RNA expression","volume":"392","author":"Grimm","year":"2005","journal-title":"Methods Enzymol"},{"key":"2024121021335928000_ref33","doi-asserted-by":"crossref","first-page":"e75894","DOI":"10.1371\/journal.pone.0075894","article-title":"Systemic delivery of shRNA by AAV9 provides highly efficient knockdown of ubiquitously expressed GFP in mouse heart, but not liver","volume":"8","author":"Piras","year":"2013","journal-title":"PLoS One"},{"key":"2024121021335928000_ref34","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.3389\/fimmu.2018.01935","article-title":"Immunoadsorption of desmoglein-3-specific IgG abolishes the blister-inducing capacity of pemphigus vulgaris IgG in neonatal mice","volume":"9","author":"Hofrichter","year":"2018","journal-title":"Front Immunol"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/33\/24\/2133\/60967080\/ddae090.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/33\/24\/2133\/60967080\/ddae090.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T21:55:20Z","timestamp":1733867720000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/33\/24\/2133\/7848472"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,29]]},"references-count":34,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,10,29]]},"published-print":{"date-parts":[[2024,12,6]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddae090","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,12,15]]},"published":{"date-parts":[[2024,10,29]]}}}