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. 2024 Mar 10;16(4):870–884. doi: 10.1038/s44321-024-00048-8

Figure 4. Antivirals are a novel class of compounds with anti-fibrotic effects in RDEB.

Figure 4

(A) Graph of time to matrix detachment in RDEB fibroblast populations comparing vehicle control (n = 13, 5 biological replicates in 2–3 technical replicates) to 1 µM idoxuridine (n = 6, 5 biological replicates in 1–2 technical replicates) and daclatasvir (n = 6, 5 biological replicates in 1–2 technical replicates) treatment. Kruskal–Wallis test with Dunn’s correction performed for significance. (B) Line graph of RDEB cell proliferation (mean ± SEM) as a percentage compared to Day 1 with vehicle control (n = 10, 5 biological replicates in duplicate), idoxuridine (n = 10, 5 biological replicates in duplicate), and daclatasvir (n = 10, 5 biological replicates in duplicate). Ordinary one-way ANOVA with Dunnett test performed. (C) Western blots of collagen I, p-AKT, p-SMAD3, and GAPDH in RDEB fibroblasts with vehicle control, exogenous TGFβ, SB431542, idoxuridine, and daclatasvir treatment (left) and quantification of blots presented as graphs of collagen I (n = 5 biological replicates), p-AKT (n = 7 biological replicates), and p-SMAD3 (n = 5 biological replicates) relative to GAPDH. RM one-way ANOVA with Holm–Šídák test for p-AKT and p-SMAD3 and Dunnett test for collagen I. (D) qPCR result of COL1A1 mRNA presented as graph of Fold Change relative to GAPDH mRNA in RDEB fibroblasts (n = 5 biological replicates) with vehicle control, idoxuridine, and daclatasvir. RM one-way ANOVA with Holm–Šídák test for significance. (E) Graph of total hydroxyproline amount (mean ± SEM) in cell layer and media of RDEB (n = 6 biological replicates), RDEB + idoxuridine (n = 6 biological replicates), RDEB + Daclatasvir (n = 6 biological replicates), non-EB (n = 6 biological replicates), EB + idoxuridine (n = 6 biological replicates), and non-EB + Daclatasvir (n = 6 biological replicates) treatment. (F) Graph of elastic modulus of RDEB matrix with vehicle control (n = 36, 3 biological replicates in 12 technical replicates), idoxuridine (n = 37, 3 biological replicates in 12 technical replicates), and daclatasvir (n = 36, 3 biological replicates in 12 technical replicates) treatment. Kruskal–Wallis test with Dunn’s correction performed for significance. Data information: In (A, C, D, F), data are presented as mean ± SEM. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, P > 0.05 is not significant (ns). Source data are available online for this figure.