{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T10:34:59Z","timestamp":1763202899904,"version":"3.28.0"},"reference-count":22,"publisher":"Scientific Scholar","content-domain":{"domain":["ijdvl.com"],"crossmark-restriction":true},"short-container-title":["Indian J Dermatol Venereol Leprol"],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Hailey\u2013Hailey disease (HHD) is a rare, autosomal dominant, hereditary skin disorder characterised by epidermal acantholysis. The HHD-associated gene ATPase calcium-transporting type 2C member 1 (<jats:italic>ATP2C1<\/jats:italic>) encodes the protein secretory pathway Ca<jats:sup>2+<\/jats:sup> ATPase1 (SPCA1), playing a critical role in HHD pathogenesis.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Aims<\/jats:title>\n<jats:p>We aimed to investigate the effect of <jats:italic>ATP2C1<\/jats:italic> knockdown on keratinocytes that mimicked acantholysis in HHD. <\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Immunohistochemistry (IHC) was employed to evaluate the levels of cytoskeletal and tight junction proteins such as SPCA1, P-cofilin, F-actin, claudins, occludin, and zonula occludens 1 in the skin biopsies of patients with HHD. Subsequently, the expression of these proteins in cultured <jats:italic>ATP2C1<\/jats:italic> knockdown keratinocytes was analysed using Western blotting and immunofluorescence. Furthermore, we assessed the proliferation, apoptosis, and intracellular Ca<jats:sup>2+<\/jats:sup> concentrations in the <jats:italic>ATP2C1<\/jats:italic>-knocked keratinocytes.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The results showed decreased levels of these proteins (SPCA1, P-cofilin, F-actin, claudins, occluding, and zonula occludens 1) in HHD skin lesions. Moreover, their levels decreased in human keratinocytes transfected with <jats:italic>ATP2C1<\/jats:italic> short hairpin RNA, accompanied by morphological acantholysis. Furthermore, the proliferation and apoptosis of the keratinocytes, as well as intracellular calcium concentrations in these cells, were not affected.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Limitations<\/jats:title>\n<jats:p>The limitations of this study are the absence of animal experiments and the failure to explore the relationship between skeletal and tight junction proteins.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The present study indicated that <jats:italic>ATP2C1<\/jats:italic> inhibition led to abnormal levels of the cytoskeletal and tight junction proteins in the keratinocytes. Therefore, keratinocytes can mimic HHD-like acantholysis and serve as an <jats:italic>in vitro<\/jats:italic> model, helping develop treatment strategies against HHD.<\/jats:p>\n<\/jats:sec>","DOI":"10.25259\/ijdvl_853_2023","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T11:38:25Z","timestamp":1715773105000},"page":"722-730","update-policy":"http:\/\/dx.doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["ATP2C1 knockdown induces abnormal expressions of cytoskeletal and tight junction proteins mimicking Hailey\u2013Hailey disease"],"prefix":"10.25259","volume":"90","author":[{"given":"Mingzhu","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Dermatology, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiran","family":"Kang","sequence":"additional","affiliation":[{"name":"Department 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