IMAGE

Fig. 7

ID
ZDB-IMAGE-160707-26
Source
Figures for Lisse et al., 2016
Image
Figure Caption

Fig. 7

Epithelial defects induced by paclitaxel are rescued upon MMP-13 inhibition. (A-C) Temporal sequence of HyPer oxidation in Tg(krt4:Gal4_tdTomato_5xUAS_HyPer) larva before and after addition of 0.01% exogenous H2O2 at 30 min, visualized as 488/405 nm emission ratio. Vehicle (0.5% DMSO) controls show some oxidation following H2O2 addition (A), which is increased after 3 h of paclitaxel incubation (B) and rescued when CL-82198 is coadministered (C). (Scale bar, 100 µm.) (D) Quantification of HyPer oxidation (n = 2, 4-5 fish per group; paclitaxel vs. paclitaxel + CL-82198; *P = 0.03). (E) Percentage of larvae with skin damage following injection of either wild-type mmp13a or mmp13aΔ373 mRNA into one-cell stage embryos and mechanical stress at 2 dpf (n = 3 biological replicates, 15 larvae per group). (F) Rescue of skin damage following pharmacological inhibition of MMP-13 and mechanical stress at 2 dpf (n = 3, 9-10 larvae per group). (G-H′′) SEM of larvae incubated for 3 h in paclitaxel + CL-82198 (G) and 96 h in vehicle (H), paclitaxel (H′), or paclitaxel + CL-82198 (H′′) shows improved skin morphology with CL-82198. [Scale bar, 25µm (G, H, and H′′) and 5 µm (H′).] (I) Model of paclitaxel-induced peripheral neuropathy. Paclitaxel damages epithelial keratinocytes by up-regulating MMP-13, leading to skin damage due to increased matrix turnover and neurotoxicity. *P < 0.05, **P < 0.01. Pctx, paclitaxel.

Acknowledgments
This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Proc. Natl. Acad. Sci. USA