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Calcineurin A‐alpha is required for the differentiation of basal keratinocyes
Author(s) -
Pena Juan Armando,
Losi Jacquelin,
Grimwood Ronald,
Guler Rebecca,
Gooch Jennifer
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1203.2
Subject(s) - calcineurin , stratum spinosum , keratin 5 , basal (medicine) , biology , keratin , microbiology and biotechnology , keratinocyte , epidermis (zoology) , cellular differentiation , endocrinology , medicine , stratum corneum , biochemistry , anatomy , in vitro , paleontology , transplantation , insulin , genetics , gene
Calcineurin is a serine/threonine phosphatase that is inhibited by the immunosuppressive agents cyclosporine A and FK506. Mice lacking the alpha isoform of the catalytic subunit of calcineurin (CnAα) have been created. On gross inspection, the skin of CnAα KO mice is noted to have decreased elasticity and resilience. Histological analyses reveal changes in the basal keratinocyte layer and an attenuation of cells in the supra‐basal layers, most notably the stratum spinosum. The calcineurin substrate NFATc is highly expressed in the nucleus of basal epidermal cells in WT mice but is cytoplasmic in KO mice, consistent with a loss of calcineurin activity in this layer. PCNA staining identified proliferating cells in the basal layer as expected, but TUNEL assay revealed increased cell death in the supra‐basal layers. Finally, immunohistochemical staining of keratins revealed that there is an increase in cells expressing the basal cell marker keratin 14 in the supra‐basal layers and a marked decrease in expression of the differentiated cell maker keratin 10 in CnAα KO mice. These findings suggest that calcineurin is required for normal differentiation of basal keratinocytes and survival of squamous epidermal cells. Interestingly, this model bears similarities to the inherited disorder Darier's disease and may shed light into the cellular basis of hyperproliferative conditions such as psoriasis.