Three stepwise pH progressions in stratum corneum for homeostatic maintenance of the skin

Author:

Fukuda Keitaro,Ito YoshihiroORCID,Furuichi Yuki,Matsui TakeshiORCID,Horikawa Hiroto,Miyano TakuyaORCID,Okada TakaharuORCID,van Logtestijn Mark,Tanaka Reiko J.ORCID,Miyawaki AtsushiORCID,Amagai MasayukiORCID

Abstract

AbstractThe stratum corneum is the outermost skin layer with a vital role in skin barrier function. It is comprised of dead keratinocytes (corneocytes) and is known to maintain its thickness by shedding cells, although, the precise mechanisms that safeguard stratum corneum maturation and homeostasis remain unclear. Previous ex vivo studies have suggested a neutral-to-acidic pH gradient in the stratum corneum. Here, we use intravital pH imaging at single-corneocyte resolution to demonstrate that corneocytes actually undergo differentiation to develop three distinct zones in the stratum corneum, each with a distinct pH value. We identified a moderately acidic lower, an acidic middle, and a pH-neutral upper layer in the stratum corneum, with tight junctions playing a key role in their development. The upper pH neutral zone can adjust its pH according to the external environment and has a neutral pH under steady-state conditions owing to the influence of skin microbiota. The middle acidic pH zone provides a defensive barrier against pathogens. With mathematical modeling, we demonstrate the controlled protease activation of kallikrein-related peptidases on the stratum corneum surface that results in proper corneocyte shedding in desquamation. This work adds crucial information to our understanding of how stratum corneum homeostasis is maintained.

Funder

Japan Agency for Medical Research and Development

MEXT | Japan Society for the Promotion of Science

Publisher

Springer Science and Business Media LLC

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. The Skin Acid Mantle: An Update on Skin pH;Journal of Investigative Dermatology;2024-09

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