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Yonsei Med J.  2013 Mar;54(2):523-528. 10.3349/ymj.2013.54.2.523.

Acute Modulations in Stratum Corneum Permeability Barrier Function Affect Claudin Expression and Epidermal Tight Junction Function via Changes of Epidermal Calcium Gradient

Affiliations
  • 1Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Korea.
  • 2Department of Dermatology, Bundang CHA Hospital, CHA University College of Medicine, Seongnam, Korea.
  • 3Division of Electron Microscopic Research, Korea Basic Science Institute, Daejeon, Korea.
  • 4Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea.
  • 5Department of Dermatology and Human Barrier Research Institute, Yonsei University College of Medicine, Seoul, Korea. ydshderm@yuhs.ac
  • 6Dermapro Skin Research Center, DERMAPRO LTD., Seoul, Korea.

Abstract

Tight junction (TJ) is recognized as a second barrier of the skin. Altered expression of TJ proteins in various skin diseases characterized by the abnormal permeability barrier such as psoriasis suggests that TJ could be affected by stratum corneum (SC) barrier status. However, the physiological relationship between SC and TJ barrier remains to be investigated. Therefore, we examined the effect of SC barrier disruption on the expression of TJ proteins, claudin (Cldn)-1 and Cldn-4, and TJ barrier function in hairless mouse skin. We also investigated whether the alterations in epidermal Ca2+ affected TJ proteins expression in vivo. Repeated tape-stripping induced a sequential change of the expression and function of TJ. As early as 15-30 minutes after tape-stripping, downregulation of Cldn-1 and Cldn-4 immunoreactivity and protein level without change in mRNA level was found. This was accompanied by the abnormal leakage of lanthanum. However, by 1 hour Cldn-1 and Cldn-4 immunolocalization recovered along with normalized lanthanum permeation pattern. Moreover, the mRNA and protein levels of Cldn-1 and Cldn-4 were increased by 1 to 6 hours after tape-stripping. Inhibition of calcium loss by immersion of barrier-disrupted skin into a high Ca2+ solution prevented the dislocation of Cldn-1 and Cldn-4. Occlusion of barrier-disrupted skin delayed the restoration of Cldn-1 and Cldn-4. Our results suggest that the alteration of epidermal Ca2+ gradient caused by SC barrier perturbation affects the TJ structure and function and the faster recovery of TJ as compared to the SC barrier may imply the protective homeostatic mechanism of skin barrier.

Keyword

Tight junction; claudin-1; claudin-4; calcium gradient; stratum corneum permeability barrier

MeSH Terms

Animals
Calcium/*metabolism
Claudin-1/genetics/*metabolism
Claudin-4/genetics/*metabolism
Epidermis/metabolism/*physiology
Female
Gene Expression Regulation
Mice
Mice, Hairless
Permeability
RNA, Messenger/metabolism
Tight Junctions/metabolism/*physiology
Claudin-1
Claudin-4
RNA, Messenger
Calcium
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