Intrinsic differences between oral and skin keratinocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE56135 | GEO | 2014/06/15
SECONDARY ACCESSION(S): PRJNA242538
REPOSITORIES: GEO
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Project description:The morphology and the behavior of skin and oral tissue keratinocytes are different. One significant dissimilarity between the two sites is the response to injury. Oral and skin keratinocytes have intrinsic differences in the response to injury and such differences are reflected in gene expression profiles. We used microarrays to investigate differences in global gene expression patterns between baseline skin and oral epithelium sheets without their underlying connective tissue. Paired skin and oral epithelium was separated from the dermis for RNA extraction and hybridization on Affymetrix microarrays. Skin epidermal tissues were obtained from the tail of mice and oral epidermal tissues were obtained from the hard palate. Enzymatically isolated epithelium was used for analysis.
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Project description:Intrinsic differences between oral and skin keratinocytes
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2009-08-12 | E-GEOD-12111 | biostudies-arrayexpress
Project description:Skin exposed to environmental threats including injuries and oxidative stress developed an efficient but not fully recognized systems of repair and antioxidant protection. In this project we provide evidence that Foxn1 in keratinocytes regulates elements of electron transport chain and participates in thioredoxin system (Txn2, Txnrd3, Srxn1) induction, particularly under hypoxic environment. It is shown that Foxn1 in keratinocytes upregulate glutathione thioredoxin reductase 3 (Txnrd3) protein, and high levels of Txnrd3 mRNA were detected in injured skin of Foxn1+/+ mice. It also shown that Foxn1 strongly downregulate CCN2 protein participating in reconstruction of the epidermis after injury. As in vitro assay revealed that Foxn1 controls keratinocytes migration stimulating it under normoxia and suppressing under hypoxia. Keratinocytes overexpressing Foxn1 and exposed to hypoxia showed reduced ability to promote angiogenesis by downregulation of Vegfa. In conclusion, this study showed a new mechanism in which Foxn1, along with hypoxia, participates in the activation of antioxidant defense and controls functional properties of keratinocytes.
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Project description:The transcription factor Interferon Regulatory Factor 6 (IRF6) is crucially involved in craniofacial development and regulates the proliferation/differentiation balance in keratinocytes. Pathological IRF6 variants have been found in Van der Woude syndrome (VWS), the most common syndromic form of cleft lip / palate (CLP) as well as in non-syndromic CLP cases. Besides its prominent function in regulating keratinocyte differentiation, recent data revealed that IRF6 is also involved in wound healing and migration. Since a significant fraction of CLP patients undergoing corrective cleft surgery experience wound healing complications, IRF6 represents an interesting candidate gene linking the two processes. However, Irf6 function has been mainly studied in mice and knowledge on IRF6 in human cells remains sparse. Here, we aimed to elucidate the role of IRF6 in human postnatal skin- and oral mucosa-derived keratinocytes by its ablation using CRISPR/Cas9. We complement this approach by applying proteomics and identify that lack of IRF6 disrupts human epithelial homeostasis by altering cell colony morphology, migration pattern, and the differentiation potential of keratinocytes.
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Project description:This was a hypothesis generating experiment to look at miR expression in a range of oral keratinocytes, including normal, precancer and oral cancer samples. The cells were cultures as per standard protocols (duplicate cultures) before assessment on the Affy miRNA array (1.0) one normal oral keratinocyte, one precancer, and 2 cancer samples, all in duplicate
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