Cytokeratin15-Positive Basal Epithelial Cells Targeted in Graft-Versus-Host Disease Express a Constitutive Antiapoptotic Phenotype
| Autor: | George F. Murphy, Robert Korngold, Thea M. Friedman, Sabina Signoretti, Diana Whitaker-Menezes, Qian Zhan |
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| Rok vydání: | 2007 |
| Předmět: |
Keratinocytes
Male Pathology medicine.medical_specialty Graft vs Host Disease Apoptosis Dermatology Biology Biochemistry Mice 03 medical and health sciences Cytokeratin Basal (phylogenetics) 0302 clinical medicine Gene expression medicine Animals Molecular Biology bcl-2-Associated X Protein 030304 developmental biology Mice Inbred BALB C 0303 health sciences integumentary system Keratin-15 Reverse Transcriptase Polymerase Chain Reaction Stem Cells Epithelial Cells Cell Biology medicine.disease Phenotype Epithelium Cell biology Mice Inbred C57BL Graft-versus-host disease medicine.anatomical_structure 030220 oncology & carcinogenesis Female Stem cell |
| Zdroj: | Journal of Investigative Dermatology. 127:106-115 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/sj.jid.5700583 |
| Popis: | The normal gene expression profile of rete-tip keratinocytes targeted in human graft-versus-host disease (GVHD) remains unexplored. Murine lingual epithelium, unlike murine skin, consists of a basal layer that resembles human cutaneous rete ridges and harbors rete tip-associated cells that express cytokeratin 15 (K15), a marker for epithelial stem cells. Target cell apoptosis in murine GVHD preferentially involves subpopulations of basal cells that (1) reside at tips of lingual rete ridge-like prominences (RLPs), (2) constitutively express K15 protein, (3) express the proapoptotic protein Bax early in disease progression, and (4) coincide spatially with putative epithelial stem cells. Here, we show by real-time reverse transcription-PCR that immunohistochemistry-guided laser-captured K15-positive (K15+) murine basal cells constitutively express quantitatively higher mRNA levels for K15 but lower mRNA levels of Bax than do K15- basal cells, consistent with the presumed stem cell nature of K15+ basal cells. Moreover, apoptosis gene array screening of K15+ microdissected basal cells demonstrated a dominant trend toward the preferential expression of genes associated with protection from apoptosis. Accordingly, genes that regulate apoptotic vulnerability are differentially expressed in basal layer subpopulations distinguishable by K15 expression. |
| Databáze: | OpenAIRE |
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