Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Article Title: Aberrant Chitinase 3-Like 1 Expression in Basal Cells Contributes to Systemic Sclerosis Fibrosis.

doi: 10.1002/advs.202310169

Figure Lengend Snippet: Figure 5. Chi3L1 activates SSc DFs via interacting with IL-17RA to further initiate NF-kB and MAPK pathways. A) Schematic overview of proteomics. B) PLS-DA of proteomic profiling between Chi3L1 and control group. C) Volcano plots of of DEPs. D) Enriched GO terms by MF. Area represents enrichments. E) Primary BP in the DEPs. The clusters are referred to BP terms. Each dot represents a single DEP. F) Cytoscape analysis of protein- protein interactions network. G) Signaling pathway classification according to KEGG terms. H) GSEA analysis via Reactome database. I) IPA of the DEPs. J) Representative WB images of indicated proteins in corresponding groups. K) Surface diagram of the docking model and their interfacing residues

Article Snippet: To assess the impact of blocking IL-17RA, the anti-IL-17RA monoclonal antibody Brodalumab (MedChemExpress) or mouse IgG1 kappa isotype control (eBioscience) was subcutaneously injected at a dose of 200 μg every 7th day (days 1, 8, and 15), with daily administration of BLM for 3 weeks (day 1 to day 21).

Techniques: Control, Protein-Protein interactions

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Article Title: Aberrant Chitinase 3-Like 1 Expression in Basal Cells Contributes to Systemic Sclerosis Fibrosis.

doi: 10.1002/advs.202310169

Figure Lengend Snippet: Figure 6. Chi3L1 activates SSc DFs through IL-17RA-dependent NF-kB and MAPK pathways. A) Schematic of the experimental protocol. B) Representative immunofluorescent staining images with Ki67 at 24 h after rChi3L1 treatment. Quantification is shown on the right. n = 6/ea. C) Representative images and quantification of transwell assay at 24 h with rChi3L1 stimulation. n = 6/ea. D) Representative images and relative quantification of collagen gel contractility assay after 24 h of rChi3L1 administration. n = 6/ea. E) Representative force-separation curve of DFs after stimulation. Relative quantification of the cell Young’s modulus is on the right. n = 6/ea. F) Relative fold change of indicated mRNA expression level in corresponding groups. n = 6/ea. G) Representative WB results and relative quantification of 𝛼-SMA and Col1A1. n = 6/ea. H) Representative immunofluorescence micrographs of DFs stained with indicated antibodies after administration. Data are presented as mean ± SEM. B, C, D, E, F and G, by one-way ANOVA followed by Bonferroni post hoc test. ns = no significance, *p < 0.05, ***p < 0.001 compared with corresponding groups.

Article Snippet: To assess the impact of blocking IL-17RA, the anti-IL-17RA monoclonal antibody Brodalumab (MedChemExpress) or mouse IgG1 kappa isotype control (eBioscience) was subcutaneously injected at a dose of 200 μg every 7th day (days 1, 8, and 15), with daily administration of BLM for 3 weeks (day 1 to day 21).

Techniques: Staining, Transwell Assay, Expressing

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Article Title: Aberrant Chitinase 3-Like 1 Expression in Basal Cells Contributes to Systemic Sclerosis Fibrosis.

doi: 10.1002/advs.202310169

Figure Lengend Snippet: Figure 7. Anti-IL-17RA mAb ameliorates fibrosis in BLM-SSc mice. A) Diagram of the experimental protocol. QW, once a week. B) Representative skin ultrasound images in corresponding groups. Quantification of dermal thickness is shown on the right. n = 6/ea. C) (i) Representative HE (left) and Masson (right) staining of skin corresponding groups. (ii) Quantification of dermal thickness. (iii) Hydroxyproline contents of skin samples. n = 6/ea. D) Representative force-displacement curve of dorsal skin in different groups. Relative quantification of the skin Young’s modulus is on the right. n = 6/ea. E) (i) AFM morphology of dermal collagen fibers. (ii) Corresponding AFM property maps. (iii) Quantification of the fibers Young’s modulus. n = 6/ea. F) Representative WB images and relative quantification of indicated proteins in skin samples of each group. n = 6/ea. G) Representative immunofluorescence images of skin stained with indicated antibodies in corresponding groups. Data are presented as mean ± SEM. B, C, D, E and F by one-way ANOVA followed by Bonferroni post hoc test. **p < 0.01, ***p < 0.001 compared with corresponding groups.

Article Snippet: To assess the impact of blocking IL-17RA, the anti-IL-17RA monoclonal antibody Brodalumab (MedChemExpress) or mouse IgG1 kappa isotype control (eBioscience) was subcutaneously injected at a dose of 200 μg every 7th day (days 1, 8, and 15), with daily administration of BLM for 3 weeks (day 1 to day 21).

Techniques: Staining

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Article Title: Aberrant Chitinase 3-Like 1 Expression in Basal Cells Contributes to Systemic Sclerosis Fibrosis.

doi: 10.1002/advs.202310169

Figure Lengend Snippet: Figure 8. A proposed model of how Chi3L1 promotes fibrosis in SSc. SSc triggers sustainable and complicated inflammation process, possibly inducing the enrichment of basal cells with high expression of Chi3L1. Chi3L1 promotes fibrosis in SSc primarily via activating fibroblasts. Mechanistically, Chi3L1 directly interacts with IL-17RA on fibroblasts, which in turn activates downstream NF-kB and MAPK pathways, thereby upregulates fibrosis-related genes, ultimately leading to enhancement of differentiation into myofibroblasts and detrimental collagen-rich ECM.

Article Snippet: To assess the impact of blocking IL-17RA, the anti-IL-17RA monoclonal antibody Brodalumab (MedChemExpress) or mouse IgG1 kappa isotype control (eBioscience) was subcutaneously injected at a dose of 200 μg every 7th day (days 1, 8, and 15), with daily administration of BLM for 3 weeks (day 1 to day 21).

Techniques: Expressing