A Keratinocyte Hypermotility/Growth-Arrest Response Involving Laminin 5 and p16INK4A Activated in Wound Healing and Senescence

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Cell Injury, Repair, Aging and Apoptosis A Keratinocyte Hypermotility/Growth-Arrest Response Involving Laminin 5 and p16 Activated in Wound Healing and Senescence

Easwar Natarajan,* John D. Omobono II,* Zongyou Guo,* Susan Hopkinson, Alexander J.F. Lazar, Thomas Brenn, Jonathan C. Jones, and James G. Rheinwald* From the Departments of Dermatology * and Pathology, Brigham and Women’s Hospital, Harvard Skin Disease Research Center, Harvard Medical School, Boston, Massachusetts; and the Department of Cell and Molecular Biology, Northwestern University Medic...

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Co-expression of p16INK4A and laminin 5 by keratinocytes: a wound-healing response coupling hypermotility with growth arrest that goes awry during epithelial neoplastic progression.

The replicative lifespan of human keratinocytes in culture is restricted by a telomere-unrelated induction of p16INK4A (p16) and p14ARF. We have found that, in vivo, p16 is expressed by epidermal and oral keratinocytes at the migrating fronts of healing wounds and at the stromal interface of severely dysplastic and early invasive lesions and that such cells also invariably display increased exp...

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Wound re-epithelialization: modulating keratinocyte migration in wound healing.

An essential feature of a healed wound is the restoration of an intact epidermal barrier through wound epithelialization, also known as re-epithelialization. The directed migration of keratinocytes is critical to wound epithelialization and defects in this function are associated with the clinical phenotype of chronic non-healing wounds. A complex balance of signaling factors and surface protei...

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Cellular senescence controls fibrosis in wound healing

Mammalian wound healing involves the rapid synthesis and deposition of extracellular matrix (ECM) to maintain tissue integrity during repair. This process must be tightly controlled, as its deregulation may result in fibrosis, scarring, and loss of tissue function. Recent studies have uncovered an efficient and parsimonious mechanism for rendering fibrogenesis self-limiting in wound healing: in...

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Erk5 controls Slug expression and keratinocyte activation during wound healing.

Reepithelialization during cutaneous wound healing involves numerous signals that result in basal keratinocyte activation, spreading, and migration, all linked to a loosening of cell-cell adhesion structures. The transcription factor Slug is required for this process, and EGF treatment of human keratinocytes induced activating phosphorylation of Erk5 that coincides with slug transcription. Acco...

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ژورنال

عنوان ژورنال: The American Journal of Pathology

سال: 2006

ISSN: 0002-9440

DOI: 10.2353/ajpath.2006.051027