764 A role for STIM1 in regulating abnormally differentiating keratinocytes in the epidermis of systemic sclerosis by integrin β4/ ERK/c-fos signaling pathway

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