Project 08
Activation of mesenchymal cells through FHL2- and FHL3-signaling during intestinal wound healing
Study group Kirfel/Büttner
Institute of Pathology
Sigmund-Freud-Str. 25 l 53105 Bonn
Extracellularly triggered signal transduction pathways induce activation and regulated migration of mesenchymal cells into wounds.
We have recently identified a novel signal transduction pathway, which involves binding of sphingosin-1-phosphate to transmembraneous receptors, subsequent activation of Rho-GTPases and translocation of the four-and-a-half-LIM-domain proteins FHL2 and FHL3 from focal adhesion into the cell nucleus. The aim of our project is to investigate the role of FHL2/3-signalling for intestinal wound healing and subsequent repair and further to identify target genes of the transcriptional coactivators FHL2/3 which are relevant for repair.
We therefore first plan to compare intestinal repair in wild-type and FHL-knockout mice and to characterise transdifferentiation of myofibroblast-like cells during wound healing. Secondly, we aim to hybridise cDNA microarrays with RNA from intestinal wounds of wild-type and knockout mice in order to identify differentially regulated genes. Finally, we will then analyse these genes in human tissue specimens obtained from patients with normal and compromised intestinal repair.