K15 Expression Implies Lateral Differentiation within Stratified Epithelial Basal Cells

Abstract

SUMMARY:Keratins are intermediate filament proteins whose expression in epithelial tissues is closely linked to their differentiated state. The greatest complexity of this expression is seen in the epidermis and associated structures. The critical basal (proliferative) cell layer expresses the major keratin pair, K5 and K14, but it also expresses an additional type I keratin, K15, about which far less is known. We have compared the expression of K15 with K14 in normal, pathological, and tissue culture contexts; distinct differences in their expression patterns have been observed that imply different regulation and function for these two genes. K15 appears to be preferentially expressed in stable or slowly turning over basal cells. In steady-state epidermis, K15 is present in higher amounts in basal cells of thin skin but in lower amounts in the rapidly turning over thick plantar skin. Although remaining high in basal cell carcinomas (noninvasive) it is suppressed in squamous cell carcinomas (which frequently metastasize). Wounding-stimulated epidermis loses K15 expression, whereas K14 is unchanged. In cultured keratinocytes, K15 levels are suppressed until the culture stratifies, whereas K14 is constitutively expressed throughout. Therefore, unlike K14, which appears to be a fundamental component of all keratinocytes, K15 expression appears to be more tightly coupled to a mature basal keratinocyte phenotype. (Lab Invest 2000, 80:1701-1710.

Re-Assessing K15 as an Epidermal Stem Cell Marker

“…As indicated earlier, some caution is required in use of K15 as a putative stem cell marker, since its expression patterns in various normal and pathological situations has not been exhaustively investigated, in spite of the fact that it was identified in 1982 [12,30]. We therefore used K15-specific antibodies and first confirmed K15 localization in relation to another well-established developmental stagespecific keratin, K14, which delineates undifferentiated epidermal basal cells in stratified epithelia [13,26,31], in various epithelia of newborn CD1 wild type mice, including the oral epithelium ( Fig. 1a and b), tongue ( Fig.…”

In vitro keratinocyte expansion for cell transplantation therapy is associated with differentiation and loss of basal layer derived progenitor population

“…Porter et al (2000) described keratin K5 þ and K15 þ cells, in the basal membrane layer, in that they could be a potential stem cell population. Lavker postulated that stem cells would be located at a depth of the rete ridges of the basal layer being protected from the injuries (Webb et al, 2004;Porter et al, 2000;Lavker and Sun, 1983). Webb et al (2004) showed that a α6intþ/K15þ subpopulations were actually located at a depth of the rete ridges, describing these cells as a stem cell population.…”

“…The TA cells regenerate the skin by moving upwards and laterally from the stratum basale to other layers during the differentiation process. The TA cells increase their cytoplasmic size, accumulate keratin, and oils providing strength and impermeability to the skin until delamination occurs (Porter et al, 2000) (Fig. 1).…”

“…Stratum basale Part of cytoskeleton keratin Webb et al (2004), Porter et al (2000), Waseem et al (1999), and Abbas et al (2011) for phenotype analysis in biopsies sections before testing in flow cytometry analysis and afterwards checking for gene expression analysis using RT-PCR. Immunofluorescence staining showed that one week cultured keratinocytes were positive for K15 and K5 stem cell markers (Fig.…”

Impact de l'interféron gamma sur la production de la kératine 15 dans les kératinocytes isolés de la peau de patients atteints d'épidermolyse bulleuse simplex /

“…En effet, sa production augmente dans le cas du carcinome basocellulaire mais elle est supprimée dans les carcinomes épidermoïdes, le psoriasis et dans des 64 conditions hyperproliférantes de l'épiderme (cicatrisation des plaies) (Porter et al, 2000;Waseem et al, 1999), La régulation à la baisse de Kl5 dans les maladies inflammatoires est liée à la préactivation des kératinocytes sous l'effet d'une production accrue de cytokines et de facteurs de croissance tel que transforming growth factor-beta (TGF-p), tumor necrosis factor-alpha (TNF-a) et epidermal growth factor (EGF) (Werner and Munz, 2000). Sous l'effet de cette production, les kératinocytes migrent vers les couches supérieures de l'épiderme pour produire d'autres kératines (Kl, K10, K16, K17) en réponse au signal d'activation (Waseem et al, 1999).…”