RT Journal Article
SR Electronic
T1 MicroRNA-155 controls pulmonary artery fibroblast cell signalling and proliferation in a knockout mouse model: A role in pulmonary arterial hypertension
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P2359
VO 44
IS Suppl 58
A1 McGlinchey, Neil
A1 Bradley, Connor
A1 McSharry, Charles
A1 Peacock, Andrew
A1 Welsh, David
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P2359.abstract
AB BackgroundFibroblast proliferation mediated by p38 mitogen-activated protein kinase (p38MAPK) signalling contributes to adventitial thickening in experimental models of pulmonary arterial hypertension (PAH). MicroRNA-155 (miR-155) over expression can down regulate Smad5, a key signalling molecule in the Bone Morphogenetic Protein type-2 receptor (BMPR2) pathway, thereby potentially mimicking the loss-of-function BMPR2 mutations that can cause PAH.AimsWe hypothesised that miR-155 down regulation would protect against enhanced hypoxic fibroblast proliferation by altering Smad5 and p38MAPK pathway activity.MethodsPulmonary adventitial fibroblasts (PAFs) isolated from miR-155 knockout (miR-155-/-) and wild-type (WT) mice were cultured in normoxia and hypoxia at various serum concentrations. Smad5 and p38MAPK expression was detected by Western blotting. Proliferation was assessed by [3H] Thymidine incorporation.ResultsmiR-/- fibroblasts showed less p38 MAPK activity (phosphorylation) in hypoxia (see Fig. 1) and increased Smad5 signalling compared with WT cells.WT fibroblasts proliferated to a higher degree in hypoxic conditions compared to normoxic controls. This effect was abrogated in the miR-155-/- cells.ConclusionmiR-155 may play a role in the pathogenesis of PAH via its control of key signalling pathways linked to pulmonary vascular remodelling.