A potential new approach for treating systemic sclerosis: Dedifferentiation of SSc fibroblasts and change in the microenvironment by blocking store-operated Ca2+ entry
Fig 2
Intracellular Ca2+ elevation from SOCE stimulated the pathological signaling pathways in SSc fibroblasts.
(A) Comparison of SOCE activity between normal adjacent fibroblasts and SSc fibroblasts in three groups. After application of thapsigargin (TG) (black arrow) to activate store-operated Ca2+ channels in Ca2+-free balanced salt solution (thick white bar), extracellular CaCl2 was added (thick black bar) to induce intracellular Ca2+ entry. Treatment with the SOCE inhibitors 2-aminoethoxydiphenyl borate (2APB), SKF96365 (SKF) and indomethacin (Indo). These three inhibitors each significantly limited the TG-induced SOCE activity in SSc fibroblasts. (B) Mean area under the intracellular Ca2+ response curves after the addition of extracellular CaCl2 in (A) (n >200 cells; mean ± SD, **, p<0.01; ***, p<0.001).