The skin exposome. UVB induced senescent signalling from dermal papilla cells, alters keratinocytes plasticity and improves in vitro wound healing.

MARTINEZ , NAHUEL; HAGELIN KARIN; BALAÑA MARÍA EUGENIA; CERUTI, JULIETA MARÍA

Roma

Congreso; ICSA; 2025

International Cell Senescence Association

In the skin, the senescence program can be elicited by the DNA damage caused by UV radiation, resulting in detrimental (chronic inflammation, limited regenerative potential of stem cells) or beneficial (induction of cellular plasticity or tissue regeneration) effects. The hair follicle is the primary source of skin stem cells. Hair follicle stem cells (HFSC) can differentiate into epidermis, sebaceous glands or epithelial follicular cells. Interaction with inductive dermal papilla cells (DPC) plays a critical role in hair neogenesis, cyclic follicle regeneration and wound healing. We previously established an UVB induced senescence 3D model in human DPC spheroids. They show altered inductivity signalling, compromising HFSC differentiation to hair lineage. In this work we aimed to study the paracrine effect of UVB irradiated DPC senescence associated secretory phenotype (SASP) on HFSC derived keratinocytes stemness and wound healing ability. Keratinocytes cultured with conditioned medium from UVB treated DPC showed higher SA-β-galactosidase activity than those cultured with non-treated DPC medium and non conditioned medium. They also showed an upregulation of SASP genes (IL-1α, IL-1β, IL-6, MMP-1, MMP3) and diminished expression of Lamin-B1, indicating an increase in paracrine senescence. Keratinocytes proliferation was compromised when cultured with both conditioned media, however, cells cultured with UVB-treated DPC medium restored their proliferation capacity in later stages. We observed that UVB treated DPC medium induced time dependent alterations in mRNA expression of some stemness genes as K19, Nfgr and Nestin. In an in vitro scratch assay, HFSC derived keratinocytes cultured for 48h with UVB senescent DPC medium were significantly more efficient in repairing the wound than those cultured with control or non conditioned medium. Our study demonstrates that UVB-senescent DPC signalling has paracrine effects on hair follicle keratinocytes, with potential impact on hair follicle regeneration. Moreover, alteration in stemness gene expression and improvement of wound healing in scratch assay, let us infer changes in HFSC plasticity to epidermal cell fate lineage. Deep understanding of these mechanisms may allow us to improve the wound healing process, the treatment of alopecias or the skin substitute grafting.