Altered cellular phenotypes and a limited yet inflammation-focused transcriptional response induced by dexamethasone in caprine dermal papilla cells

Abstract

Abstract Glucocorticoids (GCs) serve as first-line immunosuppressive therapy for alopecia areata (AA), yet physiologically suppress hair growth and cycling. The molecular basis of this paradoxical effect remains incompletely understood, hindering optimization of GCs as.effective depilatory agents. Using transcriptomic data and immunofluorescence staining, we detected robust expression of the glucocorticoid receptor (GR, encoded by NR3C1 ) in caprine dermal papilla cells (DPCs) in vitro. At the cellular level, high-dose (10 − 4 M) dexamethasone (Dex), a synthetic GC, reduced metabolic activity and proliferation, increased the proportion of cells displaying apoptotic nuclear morphology, and skewed the cell cycle toward S-phase with concomitant G 2 decrease. At the transcriptomic level, RNA-seq identified a limited set of 373 Dex-responsive genes, including canonical GR targets (e.g., FKBP5 , PER1 , LEP ), which substantially overlapped with putative conserved targets of GR and/or the NF-κB p65 subunit ( RELA ) identified from cross-species ChIP-Atlas data. Upregulated genes featured inflammatory-response modulators (e.g., IL1R2 , CD163 , PTX3 ) and the entire cholesterol biosynthetic pathway (from HMGCS1 to DHCR24 ), whereas downregulated genes included well-characterized pro-inflammatory mediators (e.g., IL6 , CXCL8 , GROα , HGF ). Functional enrichment analysis identified both inflammatory pathways (e.g., rheumatoid arthritis) and cholesterol biosynthesis-related terms as significantly enriched. Notably, directional enrichment confirmed that inflammatory pathways were predominantly represented among downregulated DEGs, while cholesterol biosynthesis-related pathways were exclusively associated with upregulated DEGs. In addition, vascular development-related GO terms were also significantly enriched, with the contributing genes largely comprising the same set of inflammation-associated mediators-a pattern recapitulated in the PPI network, where classic inflammation genes (e.g., CXCL8 , IL6 , IL1R2 , CD163 ) clustered in a single independent network. These findings identify inflammation-associated gene expression as the predominant transcriptional signature in Dex-treated caprine DPCs. The concomitant enrichment of vascular development-related terms, driven by the same inflammation-associated mediators, represents a candidate correlate for future functional investigation. These observations provide a cellular and transcriptomic data-based insight for exploring GCs action in HF and for optimizing GCs-based depilatory strategies.

The authors' abstract, as published at the source. Scientific Reports, 2026 · DOI ↗