Fig 1: Increased expression of PDIA3 enhances TGF-β1–driven fibroblast proliferation in vitro.Full figure legend with more statistical data available in Supplemental Data 1. (A) Increased levels of cell cycle proteins cyclin D1 and PCNA in renal fibroblasts in response to TGFB1 administration. P values generated by t test. (B) MTT assay readout normalized to control group demonstrating that dual treatment with pPDIA3 and TGF-β1 results in additional proliferation compared with single TGF-β1. One-way ANOVA with Bonferroni’s correction. (C) Trypan blue assay readout normalized to control group demonstrating treatment with PDIA3 and/or TGF-β1 results in additional proliferation compared with control. One-way ANOVA with Bonferroni’s correction. (D) Trypan blue assay readout normalized to control group demonstrating treatment with Loc14 reduces cell viability. One-way ANOVA with Bonferroni’s correction. (E) Coadministration of PDIA3, TGFB1, and Loc14 to human renal fibroblasts does not alter TGFBRI synthesis. Comparisons tested using 1-way ANOVA with Bonferroni’s correction. No comparisons were statistically significant at P adj < 0.05. (F) Coadministration of pPDIA3 to TGFB1-treated fibroblasts increases p-SMAD2 synthesis. Comparisons tested using 1-way ANOVA with Bonferroni’s correction. (G) Coadministration of siRNA to TGFB1-treated fibroblasts reduces p-SMAD2 synthesis. Comparisons tested using 1-way ANOVA with Bonferroni’s correction. (H) Coadministration of PDIA3 and TGFB1 to human renal fibroblasts increases SARA and p-SMAD2 synthesis. Dual treatment with PDIA3 and TGFB1 results in a greater increase compared with either alone. This effect was abolished by Loc14 administration. Comparisons tested using 1-way ANOVA with Bonferroni’s correction. (I) Time course experiment showing increased SARA protein over time following PDIA3 administration, first detectable at 6 hours after administration. One-way ANOVA with Bonferroni’s correction. (J) siRNA to SARA results in reduced levels of p-SMAD2, such that in the presence of siRNA to SARA, TGF-β1 no longer induces p-SMAD2 production in fibroblasts. One-way ANOVA with Bonferroni’s correction. *P < 0.05.