Here, using genetic knockout cells and/or mice, we show that JNK2, but not JNK1, up-regulates the expression of HIF-1α and HIF-2α and contributes to hypoxia-induced PH and polycythemia.
In the simplest scenario, disruption of pVHL function causes a failure to degrade HIF-1 alpha resulting in accumulation of HIF-1 alpha, upregulation of downstream target genes such as EPO, and the clinical manifestation of polycythemia.
Familial and congenital polycythemias with increased EPO concentration and normal arterial oxygen saturation and oxygen dissociation kinetics represent an intriguing group of disorders wherein the molecular lesions remain obscure; however, in some instances a possibility of abnormal oxygen sensing pathway involving hypoxia inducible factor-1 (HIF-1) open an intriguing yet unexplored area of hematology and biology.