This study aims to determine fibroblast growth factor 7 (FGF7) expression levels in serum and aortic tissues of Takayasu arteritis (TAK) patients, clarify the functions of distinct fibroblast subpopulations, and investigate the mechanisms by which fibroblast-secreted FGF7 mediates vascular wall remodeling.

This study enrolled patients diagnosed with TAK from Beijing Anzhen Hospital, Capital Medical University, between January 2023 and October 2025. A total of 60 serum samples and 6 affected aortic tissue samples were collected for subsequent experimental analysis. Additionally, serum samples from 20 healthy controls and 6 normal tissue samples obtained from non-inflamed para-aortic regions were collected as control groups. Serum levels of FGF7 in the 60 TAK patients and 20 healthy controls were detected using enzyme-linked immunosorbent assay (ELISA). Single-cell RNA sequencing (scRNA-seq) and proteomic analyses were separately performed on aortic tissue samples from 6 TAK patients and 6 controls, respectively.

ScRNA-seq and Proteomics Reveal Significant Upregulation of FGF7 in Patients with TAK

ScRNA-seq of aortic specimens from three TAK patients and three healthy controls resolved eight transcriptionally distinct subsets (Figure 1a). The number of fibroblasts in the aortic tissue of TAK patients was significantly increased compared to the control group (5,794 vs. 4,129) (Figure 1b). Expression profiling of FGF family members showed that not only were more fibroblasts positive for FGF7 in TAK, but the FGF7 transcript level per fibroblast was also markedly elevated compared with controls (p < 0.001) (Figure 1c-d). 

Proteomic analysis of aortic tissues from three patients with TAK and three controls demonstrated a significant upregulation of FGF7 in the TAK group [P < 0.05, log2(FC) > 1] (Figure 1e). Following proteomic analysis, GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were performed, showing the top 20 GO terms and top 10 KEGG pathways that encompass FGF7. Significantly enriched GO terms included signal transduction, actin cytoskeleton organization, positive regulation of gene expression, endothelial cell proliferation, and extracellular region. Top KEGG pathways mainly included regulation of actin cytoskeleton, Rap1 signaling pathway, Ras signaling pathway, and MAPK signaling pathway (Figure 1f).

Serum FGF7 levels showed no significant difference between the TAK and control groups (p=0.390), nor between active and inactive TAK subgroups (p=0.991), which may be attributed to the autocrine or paracrine effects of FGF7 (Figure 1g).

Upregulation of FGF7-FGFR1 Signaling Between Fibroblasts in TAK

CellChat analysis of the transcriptomic data revealed that FGF signaling was predominantly active in the TAK group (Figure 2a). The FGF7-FGFR1 ligand-receptor pair was identified as the primary contributor to this pathway, primarily mediating communication between fibroblasts (Figure 2b-c).

After extracting the fibroblasts, we performed dimensionality reduction and clustering again. Based on the gene expression patterns of the four clusters, they were annotated as FXYD1⁺fibroblasts, IL6⁺fibroblasts, FN1⁺fibroblasts, and WNT2⁺fibroblasts (Figure 2d-e). Notably, over 99% of IL6⁺fibroblasts were distributed within the TAK group (Figure 2f). And FGF7 expression was significantly higher in IL6⁺fibroblasts than in other cell subsets (Figure 2h). CellChat analysis further demonstrated that, compared with the control group, the FGF7-FGFR1 ligand-receptor pair mainly mediated cellular communication between IL6⁺fibroblasts and both IL6⁺fibroblasts and WNT2⁺fibroblasts in the TAK group (Figure 2i).

GO enrichment analysis performed separately for each subpopulation revealed distinct functional profiles: IL6⁺fibroblasts were primarily enriched in angiogenesis-related processes such as regulation of angiogenesis and vasculature development; FN1⁺fibroblasts showed significant enrichment in extracellular matrix remodeling processes including extracellular matrix organization and cell-substrate adhesion; while WNT2⁺fibroblasts were mainly enriched in processes such as cell-substrate adhesion, regulation of cellular response to growth factors, and extracellular matrix organization (Figure 2g).

These findings imply that in the aortic tissue of TAK patients, fibroblast subpopulations interact via the FGF7-FGFR1 axis to promote vascular wall remodeling, in which angiogenesis and fibrosis may occur simultaneously.

By integrating transcriptomic and proteomic profiling of aortic tissues from TAK and control groups, we first demonstrated upregulated FGF7 in TAK patients. ScRNA-seq further suggests that IL6⁺fibroblasts secrete FGF7 via autocrine/paracrine signaling, which may activate other fibroblast subsets through FGFR1. On one hand, this process may positively regulate angiogenesis within the arterial wall; on the other hand, it may promote extracellular matrix remodeling, ultimately contributing to vascular wall remodeling in TAK.