Universität Tübingen
The role of the transcription factor SRF in the inhibition of senescence in human and porcine smooth muscle cells
Abstract
This PhD thesis deals with the role of the transcription factor SRF (serum response factor) in smooth muscle cell proliferation and cellular senescence. An siRNA approach was used to reduce SRF in human and porcine primary smooth muscle cells. These cells are much closer to the real in vivo situation than immortalized cell lines. siRNA-transfection did not lead to an interferon response. siSRF797 showed a highly specific downregulation in human as well as in porcine SMCs. Sequencing of Sus scrofa SRF showed a very high evolutionary conservation when compared to Homo sapiens. Therefore, the siRNA can be tested in the porcine animal model and later in clinical trials. Downregulation of SRF caused a block in G1/S transition. TP53 upregulation and SKP2 protein downregulation led to an increase in CDKN1B protein, which was responsible for the senescence induction. siSKP2-transfection showed a similar increase in senescent cells, but only a slight increase of CDKN1B could be determined. Therefore, the downregulation of SKP2 is not the only reason for the strong increase of CDKN1B after siSRF797-transfection. A cotransfection of siCDKN1B+siSRF797 could rescue the senescent phenotype. So in conclusion, the CDKN1B upregulation is the main inducer of senescence after downregulation of SRF. The data lead to the conclusion that SRF plays a key role in the inhibition of cellular senescence in human and porcine smooth muscle cells.
Author and committee
dc:creator, dc:contributor.*- Author
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- Konjer, Nina
Identifiers
dc:identifier.*- Identifier
- hdl:10900/43917