PANX3 Channels Regulate Architecture, Adhesion, Barrier Function, and Inflammation in the Skin

Area of Science:

• Dermatology
• Molecular Biology
• Aging Research

Background:

• The role of the channel-forming glycoprotein PANX3 in skin aging and homeostasis is largely unknown.
• PANX3 is expressed in adult skin and implicated in wound healing and keratinocyte differentiation.

Purpose of the Study:

• To investigate the function of PANX3 in maintaining skin homeostasis during the aging process.
• To characterize the effects of PANX3 deficiency on skin structure, barrier function, and inflammatory responses.

Main Methods:

• Analysis of skin from global Panx3-knockout (KO) mice of different ages and sexes.
• Transcriptomic analysis of KO epidermis.
• Assessment of keratinocyte adhesion and epidermal barrier function.
• Histological examination and evaluation of inflammatory markers.

Main Results:

• PANX3 expression increases with age in normal skin.
• Panx3 KO mice exhibited reduced dermal and hypodermal areas, with sex-specific differences.
• KO epidermis showed decreased E-cadherin stabilization and Wnt signaling, leading to impaired keratinocyte adhesion and epidermal barrier function.
• Increased inflammatory signaling and a higher incidence of dermatitis were observed in aged KO mice.

Conclusions:

• PANX3 is essential for maintaining dorsal skin architecture, cell-cell, and cell-matrix adhesion during aging.
• PANX3 plays a critical role in regulating inflammatory skin responses and preventing dermatitis in aged skin.