TRPV1 channels in skin homeostasis and disease: From sensory transduction to therapeutic targeting.

TRPV1 is a non-selective cation channel that is widely expressed in multiple skin cell types, including sensory nerve fibers, keratinocytes, immune cells and fibroblasts. It can be activated by noxious heat, acidic conditions, capsaicin and a range of endogenous inflammatory mediators. Upon activation, TRPV1 mediates Ca2+ influx, leading to neuropeptide release and the initiation of neurogenic inflammation. Under physiological conditions, in addition to its well-established roles in nociception and pruritus transmission, TRPV1 contributes to several aspects of cutaneous homeostasis, including epidermal barrier repair, wound healing and hair follicle biology. Under pathological conditions, aberrant TRPV1 expression or dysfunction has been closely associated with the development of various skin disorders, such as psoriasis, atopic dermatitis, rosacea, skin aging and melanoma. In recent years, therapeutic strategies targeting TRPV1 have shown promising potential in alleviating cutaneous hypersensitivity, suppressing pruritus and delaying skin aging. This review provides an in-depth discussion of the expression profile and activation mechanism of TRPV1 in the skin, with a particular focus on its multifaceted roles in maintaining skin homeostasis and driving disease pathogenesis and further discusses the opportunities and challenges of targeting TRPV1 for clinical translation.