Pathological MAPK activation-mediated lymphatic basement membrane disruption causes lymphangiectasia that is treatable with ravoxertinib.

ABSTRACT: Lymphangiectasia, an anomalous dilation of lymphatic vessels first described in the 17th century, is frequently associated with chylous effusion, respiratory failure, and high mortality in young patients, yet the underlying molecular pathogenesis and effective treatments remain elusive. Here, we identify an unexpected causal link between MAPK activation and defective development of the lymphatic basement membrane that drives lymphangiectasia. Human pathological tissue samples from patients diagnosed with lymphangiectasia revealed sustained MAPK activation within lymphatic endothelial cells. Endothelial KRASG12D-mediated sustained MAPK activation in newborn mice caused severe pulmonary and intercostal lymphangiectasia, accumulation of chyle in the pleural space, and complete lethality. Path

SUBMITTER: Janardhan HP 

PROVIDER: S-EPMC9536262 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature