TY  - GEN
A1  - Teichmann, Míriel Tonja
TI  - Functional characterization of the transcription factor HOXA1 and the Rho-dependent kinases ROCK I/II function during angiogenesis
N2  - The transcription factor HOXA1 belongs to the family of homeobox transcription factors, which takes up an important role in the regulation of morphogenesis as well as during embryonic development. The underlying signaling pathways and mechanisms are relatively unknown. The expression of HOXA1 in zebrafish was reported mainly in anterior regions like in the pharyngeal arch and brain regions. Moreover a high HOXA1 expression was demonstrated in breast cancer lesions.   It is shown in this thesis that HOXA1 is expressed in endothelial cells. It was demonstrated in different in vitro assays that a reduced HOXA1 expression in human umbilical vein endothelial cells (HUVEC) leads to reduced sprouting, migration and network formation. A microarray analysis with HOXA1 deficient HUVEC identified E-selectin as a target gene. E-selectin is an adhesion molecule which is involved in signal transduction processes. The expression of E-selectin was highly reduced and this was validated with RT-PCR, which showed that the expression of E-selectin was strongly reduced after the expression of HOXA1 was reduced using siRNA transfection. To show in vivo relevance additional experiments in zebrafish were done. A reduced HOXA1 expression led to vascular defects in the trunk vasculature as well as in the head vasculature. Furthermore the zebrafish show head bleeding. Thus in this part of the thesis a relevance of HOXA1 for the formation of the vasculature was shown as well as a regulatory relationship between HOXA1 and E-selectin. In the second part of this thesis it was shown that the Rho kinases ROCK I and II have an anti-angiogenic influence on the neovascularization of the retina. Isolectin staining of the retina after ROCK I and II inhibition with pharmacological inhibitors showed a more compact vascular network. Furthermore a myocardial infarction study was performed in which also ROCK I and II were inhibited pharmacological. This study shows no difference with regard to angiogenesis. 
AV  - public
ID  - heidok13793
Y1  - 2012///
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/13793/
KW  - HOXA1 
KW  -  transcriptionfactor 
KW  -  Rho-dependent kinases 
KW  -  angiogenesis
ER  -