Journal: Nature Communications
Article Title: Spatiotemporally controlled restoration of GAS6 signaling via mRNA therapy promotes scarless healing in preclinical models
doi: 10.1038/s41467-026-69540-8
Figure Lengend Snippet: TAM receptor (TYRO3, AXL, MERTK) and ligand (PROS1, GAS6) expression in: a keloid-prone ( n = 8, K) versus healthy ( n = 6, N) individual wounds ( GSE113619 ; 1st and 2nd: initial and 42-day biopsies); b normal human skin ( n = 24, NS), early (≤7 days, n = 22, EW), late (8 days–1 month, n = 29, LW), and chronic (>1 month, n = 3, CW) wounds ( GSE178411 ); c normal ( n = 5, NS), acute ( n = 5, AW), type I ( n = 5, DW Ⅰ), and type II diabetic ( n = 3, DW Ⅱ) mouse wounds ( GSE283228 ); d IFN-γ/LPS-stimulated macrophages ( n = 4; GSE53986 ). Conserved GAS6 downregulation in datasets e GSE113619 , f GSE178411 , g GSE283228 , and h GSE53986 (mean ± SD; n values as in a – d ). i – l Single-cell RNA-seq analysis of human wounds ( GSE241132 ; n = 3). i UMAP plot colored by cell type. j GAS6 expression over time. k FeaturePlot visualization of GAS6 expression at representative times. l GAS6 expression across cell types. m – o In vivo analysis of RU-301-treated mice. m Representative wound images (POD0, 3, 7, 10, 14) and H&E-stained scar (POD30); scale bars, 1 mm, 500 µm. n Relative wound area over time (Ctrl, n = 6; RU-301, n = 7). o Scar length on POD30 (Ctrl, n = 3; RU-301, n = 3). p , r Apoptosis in POD3 wounds. p Quantification of Cleaved caspase 3 MFI (Control, n = 6; RU-301, n = 5). r Representative immunofluorescence images; scale bars, 500 µm, 100 µm. q , s Macrophage migration towards POD3 dermal samples. q Quantification of migrated macrophages ( n = 3). s Representative Transwell images; scale bars, 100 µm. All quantitative data are presented as mean ± SD. Statistical significance was determined using two-tailed unpaired t-tests for comparisons between two groups or one-way ANOVA with Tukey’s post-hoc test for multi-group comparisons. n represents independent biological experiments. Ctrl control group, POD postoperative day, MFI mean fluorescence intensity. Control groups received vehicle. Source data are provided as a file.
Article Snippet: For the LNP-GAS6 mRNA therapeutic evaluation, the groups included: i. saline (I), ii. Gel (II), iii. LNP@Gel (III), iv. GAS6 mRNA-LNP@Gel (50 μg/ml) (IV), v. recombinant GAS6 protein (10 μg/ml, MedChemExpress) (V).
Techniques: Expressing, Single Cell, RNA Sequencing, In Vivo, Staining, Control, Immunofluorescence, Migration, Two Tailed Test, Fluorescence