Investigating metallopeptidase-۱ inhibitorgene (TIMP۱) in liver cancer

Background: The rising cytokine tissue inhibitor of metalloproteinases-۱ (TIMP-۱) correlates with the development of inflammatorysicknesses, which includes cancer. But, the effectsof TIMP-۱ on immune cellular activation and underlying molecularmechanisms are largely unknown. Unbiased ligand-receptor-seize-screening revealed TIMP-۱-interaction with AmyloidPrecursor Protein (APP) family individuals, specificallyAPP and Amyloid Precursor-like Protein-۲ (APLP۲), whichturned into confirmed through pull-down assays and confocalmicroscopy. We located that TIMP-۱ caused glucose uptake and proinflammatory cytokine expression in human monocytes.Materials and Methods: By studying and reviewing the articlesrelated to this topic, the results were reported in the form ofthis article. The GEO online database was used to find this dataset.GSE۲۰۰۴۰۹. The Pathway enrichment analysis was carriedout using KEGG online databases.Results: In cancer patients, TIMP-۱ expression definitely correlatedwith proinflammatory cytokine expression and strategiesassociated with monocyte activation. In liver cancer, TIMP-۱plasma levels correlated with the monocyte activation markersCD۱۶۳, and the mixed use of both clinically accessible plasmaproteins served as a powerful prognostic indicator.Conclusion: In this study, we identified APP and APLP۲ asnovel cell-surface receptors of TIMP-۱ by an unbiased LRCTriCEPSapproach, which was further validated by pull–downassays as well as confocal microscopy. In addition, we showedthat TIMP-۱ triggers the activation of human monocytes in anAPP-dependent but APLP۲-independent manner. Mechanistically,TIMP-۱ brought on monocyte activation via its C-terminaldomain and via APP as validated by using in vitro interference,in silico docking, and the employment of recombinant TIMP-۱ variants. Identification of TIMP-۱ as a trigger of monocyteactivation opens new healing views for inflammatory illnesses.

کلیدواژه ها:

liver cancer ، gene ، TIMP-۱ ، metallopeptidase-۱ inhibitor ، monocyte