Novel Insights into the Role of Keratinocytes-Expressed TRPV3 in the Skin

Abstract

TRPV3 is a non-selective cation channel that is highly expressed in keratinocytes in the skin. Traditionally, keratinocytes-expressed TRPV3 is involved in multiple physiological and pathological functions of the skin, such as itching, heat pain, and hair development. Although the underlying mechanisms by which TRPV3 functions in vivo remain obscure, recent research studies suggest that several cytokines and EGFR signaling pathways may be involved. However, there have also been other studies with opposite results that question the role of TRPV3 in heat pain. In addition, an increasing number of studies have suggested a novel role of TRPV3 in promoting skin regeneration, indicating that TRPV3 may become a new potential target for regulating skin regeneration. This paper not only reviews the role of keratinocytes-expressed TRPV3 in the physiological and pathological processes of itching, heat pain, hair development, and skin regeneration, but also reviews the relationship between TRPV3 gene mutations and skin diseases such as atopic dermatitis (AD) and Olmsted syndrome (OS). This review will lay a foundation for further developing our understanding of the mechanisms by which TRPV3 is involved in itching, heat pain, and hair development, as well as the treatments for TRPV3-related skin diseases.

Unlocking the therapeutic potential of TRPV3: Insights into thermosensation, channel modulation, and skin homeostasis involving TRPV3

“…[88] From a clinical perspective, many TRPV3 gain-of-function mutations (e.g., G573S, G573C, G573A, W692G, W692C, W692S, W521S, G568C, G568D, G568V, R416Q, R416W, Q580P, L655P, M672I, L673F, A675T, and L694P) are seen in human patients with Olmsted syndrome (OS), a hyperkeratotic skin disease. [89][90][91] Most of these variant TRPV3 channels exhibit differential elevation in basal opening probabilities and cytotoxicity. [89,92] Correspondingly, a significantly higher proportion of apoptotic keratinocytes were detected in lesions from patients with OS, suggesting that hyperkeratosis in these patients may be due to increased keratinocyte apoptosis when overactive TRPV3 channel variants are expressed.…”

Targeting Transient Receptor Potential (TRP) Channels, Mas-Related G-Protein-Coupled Receptors (Mrgprs), and Protease-Activated Receptors (PARs) to Relieve Itch

“…The human TRPV3 gene shows different degrees of sequence similar to TRPV1 and TRPV4. TRPV3 is expressed in diverse human tissues, among them the skin, DRG, spinal cord, brain, and testes [73].…”

Calcium influx-induced lytic cell death disrupts skin immune homeostasis

“…Various stimuli, including heat, natural activators, and patient-specific gain-of-function mutations, can potentially activate TRPV3 (Fig. 1a ) 3 . Upon subjecting TRPV3-expressing HeLa cells (Supplementary Fig.…”