Stress-induced premature senescence of dermal papilla cells compromises hair follicle epithelial-mesenchymal interaction

Abstract

Background: Hair follicle is miniorgan constituted by keratinocytes and its distinctive mesenchyme of dermal papilla. Its aging is characterized by organ atrophy and impaired stem cell activation and differentiation. The contribution of dermal papilla to hair follicle aging change is not well understood.

Objective: This work was aimed at exploring the possible role of premature dermal papilla senescence in the pathogenesis of hair follicle aging.

Methods: Dermal papilla cells were challenged with H₂O₂ to induce premature senescence and the proliferation, apoptosis, gene expression and protein secretion were characterized. Its effect on epithelial-mesenchymal interaction was analyzed by co-culture in vitro and implantation of protein-coated beads in vivo.

Result: Dermal papilla cells were more resistant to oxidative stress-induced apoptosis than dermal fibroblasts. The surviving dermal papilla cells showed signs of senescence but still preserved key dermal papilla signature gene expression. In addition to the failure to respond to mitogenic stimulation from keratinocytes, they lost the ability to induce hair follicle neogenesis, promoted interfollicular epidermal differentiation, inhibited follicular differentiation and, importantly, suppressed clonal growth of hair follicle stem cells. They produced higher levels of multiple inflammatory cytokines, including IL-6. Functionally, IL-6 inhibited clonal keratinocyte growth in vitro and blocked the transition from telogen to anagen in vivo.

Conclusion: Stress-induced premature dermal papilla senescence can contribute to hair follicle aging change due to compromised epithelial-mesenchymal interaction.

Keywords: Aging; Alopecia; Epithelial-mesenchymal interaction; Premature senescence; Stem cell.