Hypoxia induces up-regulation of progranulin in neuroblastoma cell lines

Progranulin (PGRN) is a widely expressed multifunctional protein, involved in regulation of cell growth and cell cycle progression with a possible involvement in neurodegeneration. We looked for PGRN regulation in three different human neuroblastoma cell lines, following exposure to two different stimuli commonly associated to neurodegeneration: hypoxia and oxidative stress. For gene and protein expression analysis we carried out a quantitative RT-PCR and western blotting analysis. We show that PGRN is strongly up-regulated by hypoxia, through the mitogen-actived protein kinase (MAPK)/extracellular signal-regulated kinase (MEK) signaling cascade. PGRN is not up-regulated by H2O2-induced oxidative stress. These results suggest that PGRN in the brain could exert a protective role against hypoxic stress, one of principal risk factors involved in frontotemporal dementia pathogenesis.

Research highlights▶ Hypoxia induces PGRN up-regulation in different human neuroblastoma cell lines. ▶ siRNA-mediated down regulation of PGRN is associated with altered cell morphology. ▶ MEK/ERK pathway inhibition reverts hypoxia-dependent PGRN up-regulation. ▶ PGRN could have an adaptative/protective role against brain hypoxia.