Fibroblasts from Patients with Melorheostosis Promote Angiogenesis in Healthy Endothelial Cells through Secreted Factors.

ABSTRACT: Melorheostosis is a rare sclerosing bone disease with associated vascular abnormalities in skin and bone, which is caused by somatic mosaic single nucleotide variations in the MAP2K1 gene, which encodes MAPK/extracellular signal‒regulated kinase (ERK) kinase 1. However, disease pathogenesis is poorly understood. Using patient-derived cells, we found that affected skin fibroblasts carrying the single nucleotide variations have increased activation of ERK1/2, which results in increased expression and secretion of proangiogenic factors, including VEGF. VEGF secretion was strongly reduced in affected cells after treatment with MAPK/ERK kinase 1 inhibitor trametinib. Treatment of healthy endothelial cells on matrigel with conditioned medium from affected fibroblasts induces the adoption of a pr

SUBMITTER: Hurley-Novatny AC 

PROVIDER: S-EPMC9388700 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature