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Idiopathic Pulmonary Fibrosis (IPF) is a rare but deadly interstitial lung disease mainly affecti... more Idiopathic Pulmonary Fibrosis (IPF) is a rare but deadly interstitial lung disease mainly affecting people over 65 years of age in its sporadic form. As the world population is ageing, IPF prevalence is increasing, warranting better therapeutic options. Decades of intense research efforts resulted in the recent marketing for IPF treatment of the tyrosine kinase inhibitor Nintedanib and the anti-fibrotic drug Pirfenidone. Both drugs have been shown to improve patients’ life expectancy but fail to stop disease progression. According to the current hypothesis, repetitive injuries to the epithelial compartment play a critical role in IPF onset by precipitating their death. In the long run, overlapping cycles of repair and damages lead to the exhaustion of the alveolar epithelium regenerative capacities and the disruption of epithelial and mesenchymal cells communication. As a result, mesenchymal cells such as fibroblasts proliferate, differentiate into myofibroblasts, become resistant t...
Biochimica et biophysica acta, Jan 21, 2015
Atherosclerosis development is associated with morphological changes to intimal cells, leading to... more Atherosclerosis development is associated with morphological changes to intimal cells, leading to a stellate cell phenotype. In this study, we aimed to determine whether and how key pro-atherogenic cytokines present in atherosclerotic plaques (IL-1β, TNFα and IFNγ) could induce this phenotype, as these molecules are known to trigger the transdifferentiation of vascular smooth muscle cells (VSMCs). We found that, IL-1β was the only major inflammatory mediator tested capable of inducing a stellate morphology in VSMCs. This finding was confirmed by staining for F-actin and vinculin at focal adhesions, as these two markers were disrupted only by IL-1β. We then investigated the possible association of this IL-1β-dependent change in morphology with an increase in intracellular cAMP concentration ([cAMP]), using the FRET-based biosensor for cAMP (T)Epac(VV). Experiments in the presence of IL-1β or medium conditioned by IL-1β-treated VSMCs and pharmacological tools demonstrated that the lon...
Idiopathic Pulmonary Fibrosis (IPF) is a rare but deadly interstitial lung disease mainly affecti... more Idiopathic Pulmonary Fibrosis (IPF) is a rare but deadly interstitial lung disease mainly affecting people over 65 years of age in its sporadic form. As the world population is ageing, IPF prevalence is increasing, warranting better therapeutic options. Decades of intense research efforts resulted in the recent marketing for IPF treatment of the tyrosine kinase inhibitor Nintedanib and the anti-fibrotic drug Pirfenidone. Both drugs have been shown to improve patients’ life expectancy but fail to stop disease progression. According to the current hypothesis, repetitive injuries to the epithelial compartment play a critical role in IPF onset by precipitating their death. In the long run, overlapping cycles of repair and damages lead to the exhaustion of the alveolar epithelium regenerative capacities and the disruption of epithelial and mesenchymal cells communication. As a result, mesenchymal cells such as fibroblasts proliferate, differentiate into myofibroblasts, become resistant t...
Biochimica et biophysica acta, Jan 21, 2015
Atherosclerosis development is associated with morphological changes to intimal cells, leading to... more Atherosclerosis development is associated with morphological changes to intimal cells, leading to a stellate cell phenotype. In this study, we aimed to determine whether and how key pro-atherogenic cytokines present in atherosclerotic plaques (IL-1β, TNFα and IFNγ) could induce this phenotype, as these molecules are known to trigger the transdifferentiation of vascular smooth muscle cells (VSMCs). We found that, IL-1β was the only major inflammatory mediator tested capable of inducing a stellate morphology in VSMCs. This finding was confirmed by staining for F-actin and vinculin at focal adhesions, as these two markers were disrupted only by IL-1β. We then investigated the possible association of this IL-1β-dependent change in morphology with an increase in intracellular cAMP concentration ([cAMP]), using the FRET-based biosensor for cAMP (T)Epac(VV). Experiments in the presence of IL-1β or medium conditioned by IL-1β-treated VSMCs and pharmacological tools demonstrated that the lon...