Cellular changes that accompany shedding of human corneocytes

Tzu Kai Lin, Debra Crumrine, Larry D. Ackerman, Juan Luis Santiago, Truus Roelandt, Yoshikazu Uchida, Melanie Hupe, Gemma Fabriàs, Jose L. Abad, Robert H. Rice, Peter M. Elias

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Corneocyte desquamation has been ascribed to the following: 1) proteolytic degradation of corneodesmosomes (CDs); 2) disorganization of extracellular lamellar bilayers; and/or 3) swell-shrinkage-slough from hydration/dehydration. To address the cellular basis for normal exfoliation, we compared changes in lamellar bilayer architecture and CD structure in D-Squame strips from the first versus fifth stripping (outer vs. mid-stratum corneum (SC), respectively) from nine normal adult forearms. Strippings were either processed for standard electron microscopy (EM) or for ruthenium-, or osmium-tetroxide vapor fixation, followed by immediate epoxy embedment, an artifact-free protocol, which, to our knowledge, is previously unreported. CDs are largely intact in the mid-SC, but replaced by electron-dense (hydrophilic) clefts (lacunae) that expand laterally, splitting lamellar arrays in the outer SC. Some undegraded desmoglein 1/desmocollin 1 redistribute uniformly into corneocyte envelopes (CEs) in the outer SC (shown by proteomics, Z-stack confocal imaging, and immunoEM). CEs then thicken, likely facilitating exfoliation by increasing corneocyte rigidity. In vapor-fixed images, hydration only altered the volume of the extracellular compartment, expanding lacunae, further separating membrane arrays. During dehydration, air replaced water, maintaining the expanded extracellular compartment. Hydration also provoked degradation of membranes by activating contiguous acidic ceramidase activity. Together, these studies identify several parallel mechanisms that orchestrate exfoliation from the surface of normal human skin.

Original languageEnglish (US)
Pages (from-to)2430-2439
Number of pages10
JournalJournal of Investigative Dermatology
Issue number10
StatePublished - Oct 2012

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology


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