FGFMIR · FGF-regulated miRNAs and their roles in skin inflammation and cancer
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2014-04-01 → 2016-03-31
- Финансиране от ЕС
- 199 318 €
- Участници
- 1
- Схема
- MC-IEF
Линиите свързват координатора с партньорите.
Накратко на български
Факторите на растежа (FGF) и техните мишени в кожата се анализират чрез модели с мишки, които развиват симптоми като атопичен дерматит. Това помага за разбирането на механизмите, които контролират предразположението към възпалителни кожни заболявания и рак.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
FGF-regulated miRNAs and their roles in skin inflammation and cancer
Novel activities of Fibroblast Growth Factors in skin homeostasis and disease Fibroblast growth factors (FGFs) are master regulators of development and tissue repair, and they are involved in the pathogenesis of several major human diseases, including inflammatory diseases. To study the mechanisms of FGF action in the skin we previously generated mice lacking FGF receptors 1 and 2 in keratinocytes of the uppermost layer of the skin, the epidermis, and in the hair follicles. These mice develop a progressive inflammatory skin disease with features resembling the severe inflammatory skin disease Atopic Dermatitis (Atopic Eczema) in humans. The phenotype only develops approximately 3 weeks after birth and therefore, young mice are ideally suited to identify and characterize the direct targets of FGF signaling in the epidermis in vivo. Upon sequencing of the RNA from the isolated epidermis of FGFR-deficient and control mice prior to the development of the phenotype we identified a large number of novel FGF target genes, of which some encode proteins and others encode non-coding ribonucleic acids. Functional analysis of a subset of these genes identified a previously unidentified FGF-mediated signaling pathway in keratinocytes, which controls the susceptibility to important skin diseases. Our findings are of high medical relevance, and we are evaluating the possibility of filing a patent application based on our findings. Additionally, a manuscript describing these findings is currently in preparation, and we expect to submit it later this year. The training of the research fellow funded by the Marie Curie fellowship was highly successful, and he was recently been invited to a Gordon Research Conference as a plenary speaker. Most importantly, he has now all the skills required for an independent scientific position.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Skin cancers are the most common types of cancer in the caucasian population, and their incidence has reached epidemic proportions. In addition to skin cancer, inflammatory skin diseases are also extremely common. For the development of novel therapies for skin diseases it is essential to unravel the mechanisms that regulate skin homeostasis and pathological alterations. Recently, the host laboratory made the surprising observation that fibroblast growth factor receptor (FGFR) signalling has a tumor-suppressive function in the epidermis, since loss of FGFR1 and FGFR2 in mouse keratinocytes resulted in the development of skin inflammation, followed by spontaneous formation of carcinomas. The goal of the proposed project is to unravel the mechanisms underlying the functions of FGFRs in the epidermis with a particular focus on micro-RNAs (miRNAs). These small RNAs are emerging as new key players in the regulation of cancer-associated pathways in various tissues. However, FGF-regulated miRNAs in the skin remain to be characterized. FGF-regulated miRNAs and their targets will be identified starting from a combination of miRNA and mRNA profiling of RNA samples from epidermis of control and FGFR mutant mice at different stages of postnatal development and of tumors. Preliminary bioinformatic analysis already identified 5 miRNAs that show significant differences in expression between mutant and control mice. Accordingly, the expression level of more than 300 mRNAs was altered. Based on these data, we will identify those miRNAs that are expressed in keratinocytes in an FGF-dependent manner and we will characterize their functions and the relevant targets in cultured keratinocytes and in normal, inflamed and tumorigenic skin in vivo. Since miRNAs have already been proven to be valuable targets for the treatment of many human diseases, the proposed project has the potential to identify new possible targets for the therapy of major human skin diseases.
Оригинален текст от CORDIS (на английски).
Участници
- EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH · ZuerichКоординаторШвейцария
Връзки
Данни: CORDIS, © Европейски съюз