Abnormal PTEN expression in portal hypertensive gastric mucosa: a key to impaired PI 3-kinase/Akt activation and delayed injury healing?

SPECIFIC AIMSThe PTEN (phosphatase and tensin homologue deleted on chromosome ten) tumor suppressor is a dual specificity phophatase that negatively regulates Akt, the effector of PI 3-kinase. The PI 3-kinase/Akt signaling pathway is integral to processes essential to tissue injury healing including cell proliferation, migration, survival, and angiogenesis. However, the relationship of PTEN to injury and injury healing remains unexplored. Portal hypertensive (PHT) gastropathy, a severe complication of portal hypertension, has impaired gastric mucosal healing but the underlying causes remain unknown. The aim of the present study was to determine whether injured PHT gastric mucosa has abnormal expression/activation of PTEN and/or impaired PI 3-kinase/Akt signaling. Because PTEN expression can be directly induced by the early growth response transcriptional factor (Egr-1), which is itself regulated by TNF-α, we investigated the possible involvement of TNF-α and Egr-1 in PTEN expression and PI 3-kinase/Akt si...