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

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

Authors: Tsugawa, K  Jones, MK  Akahoshi, T  Moon, WS  Maehara, Y  Hashizume, M  Sarfeh, IJ  Tarnawski, AS 
Citation: Tsugawa K, etal., FASEB J. 2003 Dec;17(15):2316-8. Epub 2003 Oct 2.
RGD ID: 1581280
Pubmed: (View Article at PubMed) PMID:14525948
DOI: Full-text: DOI:10.1096/fj.02-1107fje

Phosphatase and tensin homologue deleted on chromosome ten (PTEN) is a dual-specificity phosphatase that has activity toward both phosphorylated peptides and phospholipids. PTEN inhibits activation of Akt, the downstream effector of PI 3-kinase, which is integral to cell proliferation, migration, survival, and angiogenesis essential for tissue injury healing. PTEN expression and activation during injury healing remain unexplored. Portal hypertensive (PHT) gastric mucosa has impaired injury healing, but the underlying mechanisms remain unknown. We investigated whether impaired healing of injured PHT gastric mucosa is due to abnormal PTEN expression/activation that leads to decreased Akt activation. We also investigated the possible involvement of Egr-1, which regulates PTEN in some cells (e.g., fetal kidney epithelial cells), and TNF-alpha, which can induce Egr-1 expression. In PHT gastric mucosa 6 h after injury, PTEN protein levels were increased by 2.7-fold; unphosphorylated PTEN (reflecting activated PTEN) was increased by 2.4-fold; Akt phosphorylation (reflecting Akt activation) was reduced by 2-fold; and Egr-1 expression was increased by 3.3-fold vs. normal gastric mucosa. TNF-alpha neutralization reversed all of the above abnormalities in PHT gastric mucosa, reduced mucosal injury, and enhanced healing. We conclude that, in injured PHT gastric mucosa, overexpressed/activated PTEN leads to the reduced activation of the PI 3-kinase/Akt pathway that results in impaired injury healing.

Annotation

Disease Annotations    
portal hypertension  (IDA,ISO)
stomach disease  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Pten  (phosphatase and tensin homolog)

Genes (Mus musculus)
Pten  (phosphatase and tensin homolog)

Genes (Homo sapiens)
PTEN  (phosphatase and tensin homolog)


Additional Information