Holocrine Secretion Occurs outside the Tight Junction Barrier in Multicellular Glands: Lessons from Claudin-1–Deficient Mice

Toru Atsugi, Mariko Yokouchi, Takashige Hirano, Ai Hirabayashi, Toshihiro Nagai, Manabu Ohyama, Takaya Abe, Mari Kaneko, Christos C. Zouboulis, Masayuki Amagai, Akiharu Kubo

Research output: Contribution to journalArticle


Holocrine secretion is a specific mode of secretion involving secretion of entire cytoplasmic materials with remnants of dead cells, as observed in multicellular exocrine glands of reptiles, birds, and mammals. Here, we found that sebaceous glands in mice, representative of multicellular exocrine glands of mammals, exhibit a form of polarized stratified epithelium equipped with tight junctions (TJs), and found that holocrine secretion occurred outside the TJ barriers. Sebaceous glands share characteristics of stratified epithelia with interfollicular epidermis, including basal-layer–restricted cell proliferation, TJ barrier formation at a specific single layer of cells with apico-basolateral plasma membrane polarity, and cell death outside the TJ barrier. Knockout of claudin-1, a transmembrane adhesive protein in TJs, in mice caused leakage of the TJ barrier in sebaceous glands and incomplete degradation of the plasma membrane and nuclei during holocrine secretion. Claudin-1 knockout resulted in the accumulation of incompletely degenerated sebocytes in sebaceous ducts, suggesting that the TJ barrier was necessary for differentiation of holocrine secretion. The redefinition of sebaceous glands as TJ-forming stratified epithelia provides an important framework to understand the molecular mechanism of holocrine secretion.

Original languageEnglish
Pages (from-to)298-308.e5
JournalJournal of Investigative Dermatology
Issue number2
Publication statusPublished - 2020 Feb


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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