Objetivo
Objective: The mammalian gut is colonized by trillions of bacteria. These gut microbes (microbiota) have coevolved with the host and developed traits that affects host physiology. Interestingly, germ-free (GF) mice exhibit arrested intestinal vascularisation if compared to littermates that were raised in a non-sterile environment (CONV-R, conventional-raised). Intestinal colonization with a normal microbiota initiates massive formation of capillary networks in the intestine of ex-GF mice (CONV-D, conventional-derived). The underlying molecular mechanisms that lead to formation of intricate capillary networks are completely unknown and therefore intense research is needed to elucidate how gut microbes trigger the formation of capillary networks. In the outlined project we will dissect proangiogenic molecules that can be induced by colonization with a gut microbiota and thus regulate microvessel formation in the intestinal mucosa. Methods: To uncover proangiogenic genes upregulated in response to microbial colonization we will perform qRT-PCR-analyses on small intestinal tissues collected from GF and CONV-R mice. The vascular marker CD31 (PECAM-1) will be used to quantify villus vascularization by immunohistochemistry and qRT-PCR. Preliminary results: We found that microbial colonization of the intestine leads to formation of an intricate vascular network. This process could be efficiently blocked by administration of an antibody directed against Tissue Factor (TF), the initiator molecule of coagulation. A distinct set of proangiogenic genes was identified to be upregulated in a TF-dependent manner following microbial colonization. Significance: A detailed understanding on how microbes affect intestinal morphogenesis and in particular the formation of microvessels in the mucosa is of major interest, since a disturbed formation of microvessels is observed in inflammatory bowel disease. Moreover, this approach will lead to better knowledge of the wound healing process.
Ámbito científico
Convocatoria de propuestas
FP7-PEOPLE-2009-RG
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Régimen de financiación
MC-ERG - European Re-integration Grants (ERG)Coordinador
55131 Mainz
Alemania