Col17a1, encoding type XVII collagen (also known as BP180), is a critical molecule at the epidermal-dermal junction. It is involved in maintaining hair follicle stem cells (HFSCs) and keratinocyte stem cell dynamics. In the skin, it plays a vital role in processes like skin homeostasis, hair follicle maintenance, and epidermal regeneration. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying its functions [1-3].

In KO mouse models, Col17a1 deficiency recapitulates hair follicle aging, characterized by the stepwise miniaturization of hair follicles and eventual hair loss. DNA damage-induced proteolysis of COL17A1 in HFSCs triggers HFSC aging, leading to the loss of stemness signatures and epidermal commitment. Aged HFSCs are cyclically eliminated through terminal epidermal differentiation, causing hair follicle miniaturization [1]. Also, forced maintenance of COL17A1 in HFSCs can prevent this aging process, highlighting its importance in the stem-cell-centric aging program of the epithelial mini-organ. In skin regeneration, EGFR-mediated regulation of COL17A1 proteolysis affects keratinocyte stem cell motility, which is coupled with self-renewal and epidermal regeneration [2].

In conclusion, Col17a1 is essential for maintaining skin-related stem cell functions, such as those in hair follicles and the epidermis. Studies using KO mouse models have revealed its role in hair follicle aging and skin regeneration. Understanding Col17a1's functions provides potential insights into anti-aging therapies and treatments for age-associated skin regeneration impairments [1-3].

References:

1. Matsumura, Hiroyuki, Mohri, Yasuaki, Binh, Nguyen Thanh, Hoeijmakers, Jan, Nishimura, Emi K. 2016. Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis. In Science (New York, N.Y.), 351, aad4395. doi:10.1126/science.aad4395. https://pubmed.ncbi.nlm.nih.gov/26912707/

2. Nanba, Daisuke, Toki, Fujio, Asakawa, Kyosuke, Toki, Hiroshi, Nishimura, Emi K. 2021. EGFR-mediated epidermal stem cell motility drives skin regeneration through COL17A1 proteolysis. In The Journal of cell biology, 220, . doi:10.1083/jcb.202012073. https://pubmed.ncbi.nlm.nih.gov/34550317/