Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Netrins are a family of proteins that mediate axonal guidance in the central nervous system (CNS). In addition to the CNS, netrins are involved in cell adhesion, motility, proliferation, differentiation, and survival. Because these processes occur in the placenta, we raised the question of whether netrin-1 is expressed by placental cells during development. In the present study, we analyzed the spatial and temporal distribution of netrin-1 and its two receptors, DCC (deleted in colorectal cancer) and UNC5B (uncoordinated-5 homolog) in human placenta using RT-PCR, Western blotting, and immunohistochemistry analysis. We demonstrated the presence of the proteins and transcripts of netrin-1 and its receptors in placenta and cytotrophoblasts. Furthermore, using immunohistochemistry, we localized endogenous netrin-1 protein staining to villous and extravillous cytotrophoblasts, and secreted netrin-1 outside the syncytiotrophoblasts. The DCC receptor was localized to syncytiotrophoblasts and invasive extravillous cytotrophoblasts during the first trimester and at term. On the other hand, the UNC5B receptor was localized to villous and extravillous cytotrophoblasts proximal to anchoring areas during the first trimester. At term, UNC5B was observed in decidual cells and weakly in extravillous cells. The discrete pattern of netrin-1 and netrin-1 receptor distribution suggested that netrin-1 protein functions might vary with its localization in the placenta and probably with time of gestation.
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PMID:Characterization and expression of netrin-1 and its receptors UNC5B and DCC in human placenta. 1982 74

Netrin-1 regulates cell survival and apoptosis by activation of its receptors, including UNC5B. However, the in vivo role of UNC5B in cell survival during cellular stress and tissue injury is unknown. We investigated the role of UNC5B in cell survival in response to stress using mice heterozygously expressing the UNC5B gene (UNC5B(-/flox)) and mice with targeted homozygous deletion of UNC5B in kidney epithelial cells (UNC5B(-/flox/GGT-cre)). Mice were subjected to two different models of organ injury: ischemia reperfusion injury of the kidney and cisplatin-induced nephrotoxicity. Both mouse models of UNC5B depletion had normal organ function and histology under basal conditions. After AKI, however, UNC5B(-/flox/GGT-cre) mice exhibited significantly worse renal function and damage, increased tubular apoptosis, enhanced p53 activation, and exacerbated inflammation compared with UNC5B(-/flox) and wild-type mice. shRNA-mediated suppression of UNC5B expression in cultured tubular epithelial cells exacerbated cisplatin-induced cell death in a p53-dependent manner and blunted Akt phosphorylation. Inhibition of PI3 kinase similarly exacerbated cisplatin-induced apoptosis; in contrast, overexpression of UNC5B reduced cisplatin-induced apoptosis in these cells. Taken together, these results show that the netrin-1 receptor UNC5B plays a critical role in cell survival and kidney injury through Akt-mediated inactivation of p53 in response to stress.
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PMID:UNC5B receptor deletion exacerbates tissue injury in response to AKI. 2411 77