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. 2022 Mar 24;11:e72443. doi: 10.7554/eLife.72443

Figure 6. Prophylactic application of Rosi prevents skin toxicities.

(A) Representative photos of rash from Vehicle- and Rosi-treated rats. (B) Rash grade. (C) Rash occurrence. (D) Body weight change. (E) H&E staining of skin biopsies. Scale bars: 200 μm. (F) Number of hair follicles in anagen phase. (G) Immunostaining for pEGFR, pERK, and Ki67 in skin biopsies from Vehicle- and Rosi-treated rats. n = 3 per group. Scale bars: 500 μm. (H) Immunostaining for Caveolin-1. Scale bars: 130 μm. (I) Relative expression of adipogenic genes in isolated dWAT cells after Vehicle or Rosi treatment. n = 3. (J) S. aureus growth in media supplemented with skin homogenates from Vehicle- or Rosi-treated rats. n = 5 per group. Data are presented as the means ± SEM. *p < 0.05, **p < 0.01, and ***p < 0.001 (Rosi group vs Vehicle group) using two-tailed unpaired Student’s t test.

Figure 6.

Figure 6—figure supplement 1. Additional effects of Rosi prevention in Afa-treated rats.

Figure 6—figure supplement 1.

(A) PPARγ, Perilipin-2 staining of skin biopsies from Ctrl, Afa-Vehicle, Afa-Rosi rats at day 10. Scale bar: 100 μm. (B) Western-blotting images and quantifications of lipases in dFB-derived adipocytes stimulated by rat skin homogenates. n = 3 per group. (C) FACS analysis of APs. (D) Quantification of APs. (E) Serum lipids of Ctrl, Afa-Vehicle and Afa-Rosi groups. GLU refers to glucose, HDL-C refers to high-density lipoproteincholesterol, LDL-C refers to low-density lipoproteincholesterol, LP (a) refers to lipoprotein (a), TC refers to total cholesterol, TG refers to triglyceride. n = 5 per group. (F) RT-PCR measurements of mRNA levels of inflammatory genes in skin tissues from Ctrl, Afa-Vehicle, and Afa-Rosi rats. n = 5 per group. (G) IL6, CD11b, CD3 (T cell), CD68 (macrophage), and toluidine blue (TB, mastocyte) staining of skin biopsies from Ctrl, Afa-Vehicle, Afa-Rosi rats at day 10. Scale bar: 200 μm. (H) Quantitative analysis of toluidine blue staining. The mastocytes were counted in 200 × fields (degranulated defined as eight or more granuli). Data are presented as the means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001 (Ctrl/Rosi vs Afa) using one-way ANOVA.
Figure 6—figure supplement 1—source data 1. Original western blot data for Figure 6—figure supplement 1B.
Figure 6—figure supplement 2. Therapeutic application of Rosi ameliorates skin rash.

Figure 6—figure supplement 2.

After oral gavage of Afa, Vehicle or Rosi gel was applied topically after Grade one rash occurred. (A) Representative photos of rash from Vehicle- and Rosi-treated rats. (B) H&E, Oil Red and Caveolin-1 staining of skin biopsies. Scale bars: 200 μm, 200 μm and 100 μm (top to bottom). (C) Rash grade. (D) Body weight change. n = 8. Data are presented as the means ± SEM. *p < 0.05, ***p < 0.001 using t-test.
Figure 6—figure supplement 3. Rosi did not interfere the anti-tumor effect of EGFRI.

Figure 6—figure supplement 3.

Ctrl: mice gavaged with solvent. Afa 30 mpk (mg/kg): Mice were gavaged with Afa and topically administered vehicle gel. Afa 30 mpk +Rosi: Mice gavaged with Afa and topically administered Rosi gel. (A) Tumor volume. (B and C) Photos of nude mice (B) and tumors (C) at day 10. (D) Tumor inhibition. (E) Body weight. n = 4–6 per group. Data are presented as the means ± SEM. p < 0.05, **p < 0.01, ***p < 0.001 (Ctrl/Afa +Rosi vs Afa) using one-way ANOVA.