Abnormal Wnt and PI3Kinase Signaling in the Malformed Intestine of lama5 Deficient Mice
Autor: | Anne-Laure Bolcato-Bellemin, Bernard Jost, Dominique Bagnard, Gertraud Orend, Christiane Arnold, Olivier Lefebvre, Christine Bole-Feysot, Léa Ritié, Patricia Simon-Assmann, Michèle Kedinger, Caroline Spenlé, Annick Klein, Joël Lacroute |
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Rok vydání: | 2012 |
Předmět: |
Mouse
Organogenesis Cellular differentiation lcsh:Medicine Gene Knockout Techniques Mice Phosphatidylinositol 3-Kinases Laminin Molecular Cell Biology Intestinal Mucosa RNA Small Interfering lcsh:Science WNT Signaling Cascade Tissue homeostasis Gene knockdown Multidisciplinary Wnt signaling pathway Cell Differentiation Cell migration Animal Models Signaling Cascades Extracellular Matrix Cell biology Intestines Medicine Small Intestine Genetic Engineering Research Article Biotechnology Signal Transduction Gastroenterology and Hepatology Biology Model Organisms Cell Adhesion Animals Humans Cell adhesion PI3K/AKT/mTOR pathway Muscle Cells lcsh:R Wnt Proteins biology.protein lcsh:Q Transcriptome Proto-Oncogene Proteins c-akt Biomarkers Transgenics Developmental Biology |
Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 5, p e37710 (2012) |
ISSN: | 1932-6203 |
Popis: | Laminins are major constituents of basement membranes and are essential for tissue homeostasis. Laminin-511 is highly expressed in the intestine and its absence causes severe malformation of the intestine and embryonic lethality. To understand the mechanistic role of laminin-511 in tissue homeostasis, we used RNA profiling of embryonic intestinal tissue of lama5 knockout mice and identified a lama5 specific gene expression signature. By combining cell culture experiments with mediated knockdown approaches, we provide a mechanistic link between laminin α5 gene deficiency and the physiological phenotype. We show that laminin α5 plays a crucial role in both epithelial and mesenchymal cell behavior by inhibiting Wnt and activating PI3K signaling. We conclude that conflicting signals are elicited in the absence of lama5, which alter cell adhesion, migration as well as epithelial and muscle differentiation. Conversely, adhesion to laminin-511 may serve as a potent regulator of known interconnected PI3K/Akt and Wnt signaling pathways. Thus deregulated adhesion to laminin-511 may be instrumental in diseases such as human pathologies of the gut where laminin-511 is abnormally expressed as it is shown here. |
Databáze: | OpenAIRE |
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