Figure 8. PLG nanoparticles mitigate collagen production by PLG-FITC+ myofibroblasts via reduction of pSTAT.
Confluent human skin fibroblasts isolated from skin biopsy specimens from healthy control (Ctrl) individuals and patients with SSc were treated with PLG nanoparticles or PBS as Ctrl for 1 hour before bulk mRNA was isolated and subjected to genome-wide transcriptome analysis. (A) The volcano plot shows differentially up- or downregulated genes in an unsupervised cluster analysis of TGF-β pathway signature genes before and after PLG nanoparticle treatment (B) Heatmap demonstrates altered expression of genes. Red indicates higher and green indicates lower levels of gene expression. The top 50 downregulated TGF-β signature genes are listed in the table. (C) The percentage and MFI of PLG-FITC+ myofibroblasts in the lung. (D and E) The MFI and representative flow plots of pSTAT1, pSTAT3, and pSTAT5 expression in the lung fibroblasts isolated from Ctrl and PLG-FITC+–treated mice. (F) The frequency and MFI of PLG-FITC+ myofibroblasts in the skin of Ctrl and PLG-FITC–treated mice. *P < 0.05; ***P < 0.001; ****P < 0.0001 via 1-way ANOVA followed by the Šidák’s multiple comparison test. dcSSc, diffuse cutaneous systemic sclerosis; padj, adjusted P value.