TRPV3 calcium channel at the crossroads of epidermal differentiation and inflammation

Abstract

Skin acts as a crucial barrier, protecting the body from external threats through a complex interplay of physical, chemical and immunological mechanisms. The transient receptor potential vanilloid 3 (TRPV3) channel, highly expressed in epidermal keratinocytes, emerges as a key regulator of skin homeostasis, influencing both epidermal differentiation and inflammation. This review explores the multifaceted role of TRPV3, highlighting its involvement in keratinocyte terminal differentiation and its association with inflammatory skin conditions. We discuss the current understanding of TRPV3's function in epidermal differentiation, focusing on the transforming factor-α/epidermal growth factor receptor (TGF-α/EGFR) pathway and provide new avenues of exploration for potential downstream signalling cascades. We also examine how TRPV3 hyperactivity contributes to skin inflammation drawing upon evidence from genetic studies in mice and humans with inflammatory skin conditions. Finally, we address how TRPV3 inhibition through antagonist molecules or biological negative regulation could represent potential therapeutic strategies for TRPV3-mediated inflammation. Focusing on TRPV3-driven signalling networks, this review outlines its dual role in skin homeostasis and disease, and sets the stage for future investigations into its molecular and therapeutic implications.