Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the c-met proto-oncogene product, was examined by in situ hybridization in the developing and adult murine olfactory system and compared with the expression of a known activator of HGF/SF, tissue-type plasminogen activator (tPA). In the developing olfactory canal, expression of both c-met and tPA was observed in the olfactory neuroepithelium, whereas HGF/SF expression appeared to be confined to the mucosa adjacent to the neuroepithelium. During development of the olfactory bulb, HGF/SF and tPA were expressed within the rostral migratory pathway leading to the olfactory bulb, whereas c-met expression was observed in the mitral cell layer (MCL) of the olfactory bulb and in the anterior olfactory nucleus. In the adult olfactory bulb, expression of HGF/SF was restricted to the periglomerular region of the glomerular layer, whereas c-met was expressed in the MCL and olfactory nerve fiber layers (ONL). tPA expression in the adult olfactory bulb was observed in the ONL, MCL, and granule cell layers. Therefore, tPA expression was relatively coincident with the expression of HGF/SF and/or c-met in the appropriate projection patterns of the developing and adult olfactory system. In addition, antibodies against tPA inhibited the olfactory bulb extract-mediated cleavage of single-chain HGF/SF. These results suggest that tPA may play a regulatory role in the development and maintenance of the olfactory system by activating HGF/SF in the immediate vicinity of its receptor.
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PMID:Expression of hepatocyte growth factor/scatter factor, its receptor, c-met, and tissue-type plasminogen activator during development of the murine olfactory system. 882 31

Plasminogen activator inhibitor-1 (PAI-1) is an acute phase protein known to correlate with hepatic fibrosis. However, whether or not PAI-1 plays a causal role in this disease process had not been directly tested. Therefore, wild-type or PAI-1 knockout (PAI-1(-/-)) mice underwent bile duct ligation. Mice were sacrificed either 3 or 14 days after surgery for assessment of early (i.e., inflammation) and late (i.e., fibrosis) changes caused by bile duct ligation. Liver injury was determined by histopathology and plasma enzymes. Accumulation of extracellular matrix was evaluated by Sirius red staining and by measuring hydroxyproline content. Hepatic expression of PAI-1 was increased approximately 9-fold by bile duct ligation in wild-type mice. Furthermore, early liver injury and inflammation due to bile duct ligation was significantly blunted in PAI-1(-/-) mice in comparison with wild-type mice. Although PAI-1(-/-) mice were significantly protected against the accumulation of extracellular matrix caused by bile duct ligation, increases in expression of indices of stellate cell activation and collagen synthesis caused by bile duct ligation were not attenuated. Protection did, however, correlate with an elevation in hepatic activities of plasminogen activator and matrix metalloprotease activities. In contrast, the increase in tissue inhibitor of metalloproteases-1 protein, a major inhibitor of matrix metalloproteases, caused by bile duct ligation was not altered in PAI-1(-/-) mice compared with the wild-type strain. The increase in hepatic activity of urokinase-type plasminogen activator was also accompanied by more activation of the hepatocyte growth factor receptor c-Met. Taken together, these data suggest that PAI-1 plays a causal role in mediating fibrosis during cholestasis.
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PMID:Critical role of plasminogen activator inhibitor-1 in cholestatic liver injury and fibrosis. 1622 37