Role of the fibroblast in pulmonary vascular remodelling: paracrine signalling and molecular mechanisms. (360G-Wellcome-086829_Z_08_Z)
Pulmonary hypertension (PH) is a life threatening condition, for which current therapies cannot offer a cure. This is because these treatments have little effect on the underlying structural pathological changes (referred to as pulmonary vascular remodelling). All three cell types of the pulmonary artery proliferate in the remodelling process. In vitro, fibroblasts proliferate in response to hypoxia. Likewise in vivo, in a chronic hypoxic rat model of PH, PAF adopt a pro-proliferative phenotype . Both processes are p38MAP Kinase dependent. In contrast, preliminary data from our lab has shown that under conditions where smooth muscle cells (SMC) did not proliferate in response to hypoxia, a co-culture with fibroblasts initiated proliferation which was dependent on p38MAPK in the fibroblasts. My hypothesis is that hypoxia stimulates a p38MAPK dependent release of mitogen(s) from the fibroblast which are responsible for SMC proliferation. We will identify the mitogens and characterise the signalling pathway involved in this process. Both in vitro cell work and in vivo animal models will be used to address these questions.
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Grant Details
Amount Awarded | 239001 |
Applicant Surname | Church |
Approval Committee | Clinical Interview Committee |
Award Date | 2008-12-04T00:00:00+00:00 |
Financial Year | 2008/09 |
Grant Programme: Title | Research Training Fellowship |
Internal ID | 086829/Z/08/Z |
Lead Applicant | Dr Alistair Church |
Partnership Value | 239001 |
Planned Dates: End Date | 2012-04-30T00:00:00+00:00 |
Planned Dates: Start Date | 2009-05-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Scotland |
Sponsor(s) | Prof Alirio Melendez, Prof Andrew Peacock, Prof Roger Wadsworth |