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CRM 1 and chromosomal passenger complex component survivin are essential to normal mitosis progress and to preserve keratinocytes from mitotic abnormalities
Author(s) -
Labarrade F.,
Botto J.M.,
Domloge N.
Publication year - 2016
Publication title -
international journal of cosmetic science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.532
H-Index - 62
eISSN - 1468-2494
pISSN - 0142-5463
DOI - 10.1111/ics.12311
Subject(s) - mitosis , survivin , component (thermodynamics) , microbiology and biotechnology , keratinocyte , biology , genetics , physics , cell culture , thermodynamics
Objective Human epidermis provides the body a barrier against environmental assaults. To assume this function, the epidermis needs the renewal of keratinocytes allowed by constant mitosis, which replace the exfoliating corneocytes. Keratinocyte stem cells ( KSC s) located in the basal epidermis are mitotically active, self‐renewing and govern the epithelial stratification by producing renewed source of keratinocytes. Protein complex such as the chromosomal passenger complex ( CPC ) allows the correct development of this process. The CPC is composed of four members: INCENP , survivin, borealin and aurora kinase B, and the disruption of the CPC during cell division induces mitotic spindle defects and improper repartition of chromosomes. The aim of our study was to investigate the implication of CRM 1 and survivin in the progress of mitosis in skin keratinocytes. Methods Cultured human keratinocytes and skin biopsies were used in this study. KSC s‐enriched population of keratinocytes was isolated from total keratinocytes by differential attachment to a type IV collagen matrix. Survivin and CRM 1 expression levels were assessed by immunofluorescence and immunoblotting. Specific si RNA s for each CPC member and for CRM 1 were used to determine the relationship between these proteins. Survivin‐specific si RNA was used to induce the apparition of mitotic abnormalities in cultured keratinocytes. Results We demonstrated the ability of our compound ‘ IV 08.009’ to modulate the expression level of survivin and CRM 1 in keratinocytes and in skin biopsies. We observed that members of the CPC are interdependent: si RNA ‐induced inhibition of one component caused a decrease in the expression of all other CPC members. Downregulation of survivin or CRM 1 induced mitotic abnormalities in keratinocytes. However, decreased number of mitotic abnormalities was observed in keratinocytes after ‘ IV 08.009’ application. Conclusion Basal keratinocytes may divide frequently during skin lifespan, and signs of deterioration could appear such as loss of protein factors required for correct mitosis. Our findings suggest that mitotic abnormalities can be prevented by the modulation of CRM 1 and survivin. We demonstrated the ability of compound ‘ IV 08.009’ to efficiently protect cultured keratinocytes from mitotic abnormalities.