Humanization of autoantigen: 水疱性類天疱瘡の病態解明と新規治療法開発

http://www.jidonline.org/article/S0022202X21025306/pdf

Stabilization of Hemidesmosomal Proteins: A Possible Key Contributor to Wnt/β-Catenin Pathway Action in the Skin

The skin epidermis and appendages undergo ongoing renewal throughout life. Stem cells residing in the epidermis and hair follicles are pivotal for sustaining skin homeostasis. The self-renewal ability of stem cells significantly decreases during skin aging but actively increases during wound repair. Residential stem cells reside in niches that provide spatially distinct microenvironments for stem cell maintenance and function. Cell-extracellular matrix (ECM) adhesion is essential for the establishment of niche architecture. Collagen XVII (COL17), as a transmembrane protein constituting hemidesmosomes (HDs), mediates the interactions of stem cells with surrounding cells and the matrix to regulate skin homeostasis, aging and wound repair. This review focuses on the pivotal role of the niche component COL17 in stem cell maintenance and its function in regulation of skin aging and wound repair.

Targeting the stem cell niche: role of collagen XVII in skin aging and wound repair

Wnt/β-Catenin Signaling Stabilizes Hemidesmosomes in Keratinocytes.

Subepidermal blisters form through the detachment of the epidermis from the dermis. Despite such blisters being common in clinical practice, how they heal has not been fully elucidated. Here, we uncover the precise cellular contribution to subepidermal blister healing. The growth of hair follicles (HFs) was retarded during the healing processes of subepidermal blisters. The progeny of HF junctional zone stem cells (SCs), rather than those of epidermal SCs, were the main contributors to blister healing, and HF depletion from the wound bed through Col17a1 knockout verified the contribution of epidermal SC progeny. The wedge-shaped morphology of keratinocytes in the blistered skin helped cover the epidermal defects and was reduced by Col7a1 knockout or by extracellular calcium administration, resulting in delayed blister healing. These findings, corroborated by mathematical modeling and human blister samples, demonstrate that subepidermal blisters heal primarily via the replenishment of keratinocytes from HF pools at the expense of HF growth and through the proper morphological transformation of the regenerated cells. Our study paves the way for tailoring therapeutic interventions for subepidermal blistering diseases, including epidermolysis bullosa and pemphigoid diseases.

/pdf/subepidermal-blisters-are-healed-by-wedge-shaped-3gdxad9nbc.pdf

Subepidermal blisters are healed by wedge-shaped keratinocytes of hair follicle origin

The tracheal epithelium that connects the upper airway to the lung consists of two compartments, the submucosal gland (SMG) and the surface airway epithelium (SAE). Less exposed to environmental hazards, myoepithelial cells (MECs) in SMG represent a stem cell reservoir to repair severely injured surface epithelia (1,2).

/pdf/buried-myoepithelial-stem-cells-as-a-reservoir-for-repairing-4qzekdawue.pdf

Mika Watanabe

Papers

Wnt/β-Catenin Signaling Stabilizes Hemidesmosomes in Keratinocytes.

Subepidermal blisters are healed by wedge-shaped keratinocytes of hair follicle origin

Buried myoepithelial stem cells as a reservoir for repairing the exposed airway epithelium.