Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NPHS1 encodes the structural protein nephrin, which has a crucial role in the filtration barrier of the glomerular podocyte. Mutations or deregulation of NPHS1 are associated with a variety of renal diseases, including the Finnish type congenital nephrotic syndrome. This study analyzed a potential regulation of nephrin by the Wilms' tumor protein, Wt1. Using an inducible U2OS osteosarcoma cell line, it is shown that upon Wt1 induction, endogenous nephrin mRNA becomes highly upregulated. Co-transfection studies demonstrate that Wt1 can activate the nephrin promoter >10-fold. DNase footprinting and mutation analysis identify a Wt1 responsive element in the nephrin promoter, which is required for the binding of Wt1 protein. Mutations or deletion of this Wt1 responsive element completely abolished transactivation of the nephrin promoter by Wt1. Moreover, transgenic analysis demonstrates the requirement of the identified binding site to direct podocyte-specific expression of a reporter gene in transgenic mice, thus confirming the importance of this site for the regulation of nephrin in vivo. Finally, it is shown that nephrin expression is lowest in kidneys of mice that lack specifically the Wt1(-KTS) splice variant, but in comparison with wild-type littermates, it is also reduced in animals with disruption of the Wt1(+KTS) splice variant. Taken together, these data identify nephrin as a direct transcriptional target for Wt1 and underline the importance of Wt1 as a key regulator in podocyte function.
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PMID:The major podocyte protein nephrin is transcriptionally activated by the Wilms' tumor suppressor WT1. 1557 7

Melorheostosis is an uncommon, sporadic, sclerosing bone lesion that may affect the adjacent soft tissues. It has been associated with many entities such as osteopoikilosis, soft tissue vascular malformations, bone and soft tissue tumors, nephrotic syndrome, segmental limb contractures, osteosarcoma, desmoid tumor, and mesenteric fibromatosis. Synovial osteochondromatosis is a benign neoplasia of the hyaline cartilage presenting as nodules in the subsynovial tissue of a joint or tendon sheath. The intra-articular extension of melorheostosis mimicking synovial osteochondromatosis has not been reported before. In this article, the authors describe an unusual case mimicking synovial chondromatosis arising as a result of melorheostosis and their characteristic imaging findings.
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PMID:Melorheostosis mimicking synovial osteochondromatosis. 2597 32