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- W4366171914 abstract "Stratum corneum (SC), which consists of dead keratinocytes (corneocytes), maintains its thickness and functions as a skin barrier. How SC maintains its homeostasis, however, remains unclear. We speculate that the pH profile in SC impacts SC homeostasis, based on our findings that a unique cell death, called corneoptosis, of the uppermost stratum granulosum keratinocytes (SG1 cells) requires controlled intercellular acidification to convert SG1 cells into corneocytes and that SC has three stepwise pH zones (lower-moderately acidic, middle-acidic, and upper-nearly neutral zones). Here, we conducted intravital SC-pH imaging using mice expressing Venus–mCherry from SG1 (SASP-VC mice) and elucidated the biological significance of the SC-pH profile in SC homeostasis. We found that the acidic pH of SG1 cells undergoing corneoptosis was similar to that of corneocytes in the lower SC-pH zone. In contrast, the lower and middle SC-pH zones diminished, and the whole SC exhibited neutral pH when corneoptosis was impaired in the absence of a tight junction protein, claudin-1 (Cldn1), suggesting that the corneoptosis is required to keep the three stepwise pH zones. The upper SC-pH zone showed an acclimation-like property, i.e. its pH followed external pH. The neutralization of the upper SC-pH zone required skin microbiota because SASP-VC germ-free (GF) mice exhibited upper-acidic SC-pH zone, whereas SASP-VC GF mice co-housed with specific pathogen-free (SPF) mice had the similar pH to that of SPF mice. Finally, mathematical modeling indicated that the three stepwise SC-pH profiles reproduced the increased catalytic activity of kallikrein-related peptidases (KLKs) toward the SC surface. In contrast, the SC of Cldn1-/-mice resulted in insufficient KLK catalytic activity, consistent with the thick SC observed in Cldn1-/-mice. Thus, three stepwise pH zones are necessary to maintain functional SC homeostasis." @default.
- W4366171914 created "2023-04-19" @default.
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- W4366171914 date "2023-05-01" @default.
- W4366171914 modified "2023-09-28" @default.
- W4366171914 title "714 Stratum corneum homeostasis requires three-stepwise pH zones mediated by the functional cell death of keratinocytes, corneoptosis" @default.
- W4366171914 doi "https://doi.org/10.1016/j.jid.2023.03.723" @default.
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