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Diurnal variation of tight junction integrity associates inversely with matrix metalloproteinase expression in Xenopus laevis corneal epithelium: implications for circadian regulation of homeostatic surface cell desquamation.

Abstract

BACKGROUND AND OBJECTIVES

The corneal epithelium provides a protective barrier against pathogen entrance and abrasive forces, largely due to the intercellular junctional complexes between neighboring cells. After a prescribed duration at the corneal surface, tight junctions between squamous surface cells must be disrupted to enable them to desquamate as a component of the tissue homeostatic renewal. We hypothesize that matrix metalloproteinase (MMPs) are secreted by corneal epithelial cells and cleave intercellular junctional proteins extracellularly at the epithelial surface. The purpose of this study was to examine the expression of specific MMPs and tight junction proteins during both the light and dark phases of the circadian cycle, and to assess their temporal and spatial relationships in the Xenopus laevis corneal epithelium.

METHODOLOGY/PRINCIPAL FINDINGS

Expression of MMP-2, tissue inhibitor of MMP-2 (TIMP-2), membrane type 1-MMP (MT1-MMP) and the tight junction proteins occludin and claudin-4 were examined by confocal double-label immunohistochemistry on corneas obtained from Xenopus frogs at different circadian times. Occludin and claudin-4 expression was generally uniformly intact on the surface corneal epithelial cell lateral membranes during the daytime, but was frequently disrupted in small clusters of cells at night. Concomitantly, MMP-2 expression was often elevated in a mosaic pattern at nighttime and associated with clusters of desquamating surface cells. The MMP-2 binding partners, TIMP-2 and MT1-MMP were also localized to surface corneal epithelial cells during both the light and dark phases, with TIMP-2 tending to be elevated during the daytime.

CONCLUSIONS/SIGNIFICANCE

MMP-2 protein expression is elevated in a mosaic pattern in surface corneal epithelial cells during the nighttime in Xenopus laevis, and may play a role in homeostatic surface cell desquamation by disrupting intercellular junctional proteins. The sequence of MMP secretion and activation, tight junction protein cleavage, and subsequent surface cell desquamation and renewal may be orchestrated by nocturnal circadian signals.

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  • Authors+Show Affiliations

    ,

    Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.

    ,

    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, United States of America.

    Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.

    Source

    PloS one 9:11 2014 pg e113810

    MeSH

    Animals
    Circadian Rhythm
    Claudin-4
    Epithelium, Corneal
    Immunohistochemistry
    Matrix Metalloproteinase 14
    Matrix Metalloproteinase 2
    Matrix Metalloproteinases
    Microscopy, Confocal
    Occludin
    Tight Junctions
    Tissue Inhibitor of Metalloproteinase-2
    Xenopus laevis

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    25412440

    Citation

    Wiechmann, Allan F., et al. "Diurnal Variation of Tight Junction Integrity Associates Inversely With Matrix Metalloproteinase Expression in Xenopus Laevis Corneal Epithelium: Implications for Circadian Regulation of Homeostatic Surface Cell Desquamation." PloS One, vol. 9, no. 11, 2014, pp. e113810.
    Wiechmann AF, Ceresa BP, Howard EW. Diurnal variation of tight junction integrity associates inversely with matrix metalloproteinase expression in Xenopus laevis corneal epithelium: implications for circadian regulation of homeostatic surface cell desquamation. PLoS ONE. 2014;9(11):e113810.
    Wiechmann, A. F., Ceresa, B. P., & Howard, E. W. (2014). Diurnal variation of tight junction integrity associates inversely with matrix metalloproteinase expression in Xenopus laevis corneal epithelium: implications for circadian regulation of homeostatic surface cell desquamation. PloS One, 9(11), pp. e113810. doi:10.1371/journal.pone.0113810.
    Wiechmann AF, Ceresa BP, Howard EW. Diurnal Variation of Tight Junction Integrity Associates Inversely With Matrix Metalloproteinase Expression in Xenopus Laevis Corneal Epithelium: Implications for Circadian Regulation of Homeostatic Surface Cell Desquamation. PLoS ONE. 2014;9(11):e113810. PubMed PMID: 25412440.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Diurnal variation of tight junction integrity associates inversely with matrix metalloproteinase expression in Xenopus laevis corneal epithelium: implications for circadian regulation of homeostatic surface cell desquamation. AU - Wiechmann,Allan F, AU - Ceresa,Brian P, AU - Howard,Eric W, Y1 - 2014/11/20/ PY - 2014/09/24/received PY - 2014/10/31/accepted PY - 2014/11/21/entrez PY - 2014/11/21/pubmed PY - 2015/12/23/medline SP - e113810 EP - e113810 JF - PloS one JO - PLoS ONE VL - 9 IS - 11 N2 - BACKGROUND AND OBJECTIVES: The corneal epithelium provides a protective barrier against pathogen entrance and abrasive forces, largely due to the intercellular junctional complexes between neighboring cells. After a prescribed duration at the corneal surface, tight junctions between squamous surface cells must be disrupted to enable them to desquamate as a component of the tissue homeostatic renewal. We hypothesize that matrix metalloproteinase (MMPs) are secreted by corneal epithelial cells and cleave intercellular junctional proteins extracellularly at the epithelial surface. The purpose of this study was to examine the expression of specific MMPs and tight junction proteins during both the light and dark phases of the circadian cycle, and to assess their temporal and spatial relationships in the Xenopus laevis corneal epithelium. METHODOLOGY/PRINCIPAL FINDINGS: Expression of MMP-2, tissue inhibitor of MMP-2 (TIMP-2), membrane type 1-MMP (MT1-MMP) and the tight junction proteins occludin and claudin-4 were examined by confocal double-label immunohistochemistry on corneas obtained from Xenopus frogs at different circadian times. Occludin and claudin-4 expression was generally uniformly intact on the surface corneal epithelial cell lateral membranes during the daytime, but was frequently disrupted in small clusters of cells at night. Concomitantly, MMP-2 expression was often elevated in a mosaic pattern at nighttime and associated with clusters of desquamating surface cells. The MMP-2 binding partners, TIMP-2 and MT1-MMP were also localized to surface corneal epithelial cells during both the light and dark phases, with TIMP-2 tending to be elevated during the daytime. CONCLUSIONS/SIGNIFICANCE: MMP-2 protein expression is elevated in a mosaic pattern in surface corneal epithelial cells during the nighttime in Xenopus laevis, and may play a role in homeostatic surface cell desquamation by disrupting intercellular junctional proteins. The sequence of MMP secretion and activation, tight junction protein cleavage, and subsequent surface cell desquamation and renewal may be orchestrated by nocturnal circadian signals. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25412440/Diurnal_variation_of_tight_junction_integrity_associates_inversely_with_matrix_metalloproteinase_expression_in_Xenopus_laevis_corneal_epithelium:_implications_for_circadian_regulation_of_homeostatic_surface_cell_desquamation L2 - http://dx.plos.org/10.1371/journal.pone.0113810 DB - PRIME DP - Unbound Medicine ER -