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Identification and Functional Analysis of Healing Regulators in


Two major challenges in our understanding of epithelial repair and regeneration is the identification of the signals triggered after injury and the characterization of mechanisms initiated during tissue repair. From a clinical perspective, a key question that remains unanswered is “Why do some wounds fail to heal?” Considering the low genetic redundancy of Drosophila and its high degree of conservation of fundamental functions, the analysis of wound closure in imaginal discs, whose features are comparable to other post-injury events, seems to be a good model. To proceed to genomic studies, we developed a healing-permissive in vitro culture system for discs. Employing this method and microarray analysis, we aimed to identify relevant genes that are involved in healing. We compared cells that were actively involved in healing to those not involved, and identified a set of upregulated or downregulated genes. They were annotated, clustered by expression profiles, chromosomal locations, and presumptive functions. Most importantly, we functionally tested them in a healing assay. This led to the selection of a group of genes whose changes in expression level and functionality are significant for proper tissue repair. Data obtained from these analyses must facilitate the targeting of these genes in gene therapy or pharmacological studies in mammals.


Vyšlo v časopise: Identification and Functional Analysis of Healing Regulators in. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004965
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004965

Souhrn

Two major challenges in our understanding of epithelial repair and regeneration is the identification of the signals triggered after injury and the characterization of mechanisms initiated during tissue repair. From a clinical perspective, a key question that remains unanswered is “Why do some wounds fail to heal?” Considering the low genetic redundancy of Drosophila and its high degree of conservation of fundamental functions, the analysis of wound closure in imaginal discs, whose features are comparable to other post-injury events, seems to be a good model. To proceed to genomic studies, we developed a healing-permissive in vitro culture system for discs. Employing this method and microarray analysis, we aimed to identify relevant genes that are involved in healing. We compared cells that were actively involved in healing to those not involved, and identified a set of upregulated or downregulated genes. They were annotated, clustered by expression profiles, chromosomal locations, and presumptive functions. Most importantly, we functionally tested them in a healing assay. This led to the selection of a group of genes whose changes in expression level and functionality are significant for proper tissue repair. Data obtained from these analyses must facilitate the targeting of these genes in gene therapy or pharmacological studies in mammals.


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