Figure 4. BET inhibition affects Ca²⁺-related pathways and intracellular Ca²⁺ in dcSSc fibroblasts.

(A) The Ca²⁺ signaling pathway (KEGG: 04020) diagram is overlaid with the expression changes of each gene. The legend describes the values on the gradient. Downregulation is shown in blue, while upregulation is in red. For legibility, 1 gene may be presented at multiple boxes in the diagram. In addition, 1 box may represent multiple genes in the same gene family. For each gene family, the color corresponding to the gene with the highest absolute fold change is displayed. For example, the ORAI box depicts significant upregulation of ORAI1 and ORAI3 and downregulation of ORAI2. The ORAI box is shown in red because ORAI1 shows the most significant fold change among the 3. (B) All the differentially expressed genes in Ca²⁺ signaling pathway (KEGG: 04020) are ranked based on their absolute value of log fold change. Upregulated genes are shown in red, and downregulated genes are shown in blue. n = 6 patient pairs. (C) BET inhibition by JQ1 significantly reduced intracellular Ca²⁺ levels in dcSSc fibroblasts. n = 5 patients. Results are expressed as mean ± SD and P < 0.05 was considered significant. Significance was determined by paired 2-tailed t test (C). NT, no treatment.