Type XVII collagen coordinates proliferation in the interfollicular epidermis

Abstract

Type XVII collagen (COL17) is a transmembrane protein located at the epidermal basement membrane zone. COL17 deficiency results in premature hair aging phenotypes and in junctional epidermolysis bullosa. Here, we show that COL17 plays a central role in regulating interfollicular epidermis (IFE) proliferation. Loss of COL17 leads to transient IFE hypertrophy in neonatal mice owing to aberrant Wnt signaling. The replenishment of COL17 in the neonatal epidermis of COL17-null mice reverses the proliferative IFE phenotype and the altered Wnt signaling. Physical aging abolishes membranous COL17 in IFE basal cells because of inactive atypical protein kinase C signaling and also induces epidermal hyperproliferation. The overexpression of human COL17 in aged mouse epidermis suppresses IFE hypertrophy. These findings demonstrate that COL17 governs IFE proliferation of neonatal and aged skin in distinct ways. Our study indicates that COL17 could be an important target of anti-aging strategies in the skin.DOI: http://dx.doi.org/10.7554/eLife.26635.001

Life before and beyond blistering: The role of collagen XVII in epidermal physiology

“…Epidermal polarity is maintained by the fine balance between symmetrical cell division (SCD) and asymmetrical cell division (ACD) . Physiological ageing increases the ratio of ACD to SCD in the IFE, which is consistent with the phenotypes of premature ageing in mice with the epidermal‐specific deletion of atypical PKCλ (aPKCλ), a key molecule that regulates cell polarity. This is corroborated by the reduction in non‐hemidesmosomal COL17 in 3D‐reconstructed epidermis that is treated with aPKC inhibitors .…”

“…The fact that hemidesmosomes are not observed at the cell‐cell junction of keratinocytes indicates the presence of non‐hemidesmosomal COL17. Non‐hemidesmosomal COL17 is triton‐X100 soluble and is distinct from hemidesmosomal COL17, which is triton‐X100 insoluble . Non‐hemidesmosomal COL17 does not colocalize with desmosomal proteins, which are compatible with detergent‐solubility .…”

“…Non‐hemidesmosomal COL17 is triton‐X100 soluble and is distinct from hemidesmosomal COL17, which is triton‐X100 insoluble . Non‐hemidesmosomal COL17 does not colocalize with desmosomal proteins, which are compatible with detergent‐solubility . As it does not appear to be involved in epidermal‐dermal attachment, non‐hemidesmosomal COL17 might play other roles in keratinocyte physiology.…”

“…The blistering phenotypes of BP and junctional EB have highlighted COL17 as an anchor between epidermis and dermis. However, COL17 labelling in human and murine epidermis is found not only in the DEJ but also in the apicolateral plasma membrane of epidermal basal keratinocytes (Figure ). This finding has led to the classification of hemidesmosomal COL17 and non‐hemidesmosomal COL17.…”

“…As it does not appear to be involved in epidermal‐dermal attachment, non‐hemidesmosomal COL17 might play other roles in keratinocyte physiology. Recently, physiological or organismal ageing has been reported to reduce non‐hemidesmosomal COL17 in the interfollicular epidermis (IFE) (Figure ). Epidermal polarity is maintained by the fine balance between symmetrical cell division (SCD) and asymmetrical cell division (ACD) .…”