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- W4366171471 abstract "Background: Systemic sclerosis(SSc) is characterized by progressive fibrosis of the skin and internal organs. The change in the epidermal–dermal interactions potentially causes the abnormal differentiation of the SSc epidermis. However, blockage of the increased Ca2+ signaling restrains SSc pathogenesis in SSc-bleomycin mice. The activation of Ca2+ signaling facilitates the induction of keratinocyte differentiation, which is regulated by stromal interaction molecule 1 (STIM1). Thus, STIM1 may be involved in regulating abnormal differentiation of the SSc epidermis. Objectives: This study investigated the underlying mechanism of STIM1-regulated abnormal differentiation of the epidermis. Methods: The skin biopsies collected from SSc patients, healthy volunteers and SSc bleomycin mice were used to detect STIM1-regulated epidermal differentiation by H&E and IHC staining. The expression of STIM1, cytokeratin 1/10(K1/10), integrin β4(ITGB4), MAPK, and c-Fos was evaluated by IHC staining. Additionally, the combination with 2-aminoethoxydiphenyl borate(2-APB) in the mice further demonstrated the effect of STIM1-regulated Ca2+ signaling on abnormal differentiation of the epidermis. Results: In contrast to healthy volunteers, skin biopsies from SSc samples showed abnormal differentiation and an increased level of STIM1 expression in the epidermis. Similar results were detected in the SSc mouse model, in which the expression of STIM1 and K1/10 increased significantly. Treatment with 2-APB significantly restrained both the abnormal epidermal differentiation and the increased level of STIM1 and K1/10. Furthermore, STIM1-regulated abnormal differentiation of the epidermis could be due to ITGB4, MAPK and c-Fos signaling, and bleomycin-induced increased expression of ITGB4 and phospho-ERK and c-Fos translocation to nuclei were also inhibited by 2-APB in mice. Conclusion: This study demonstrated the STIM1-regulated abnormal differentiation in the SSc epidermis was dependent on ITGB4/ERK/c-Fos signaling." @default.
- W4366171471 created "2023-04-19" @default.
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- W4366171471 date "2023-05-01" @default.
- W4366171471 modified "2023-09-28" @default.
- W4366171471 title "764 A role for STIM1 in regulating abnormally differentiating keratinocytes in the epidermis of systemic sclerosis by integrin β4/ ERK/c-fos signaling pathway" @default.
- W4366171471 doi "https://doi.org/10.1016/j.jid.2023.03.773" @default.
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