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- W2084998185 abstract "Mutations of the tumor suppressor gene von Hippel-Lindau (VHL) can lead to benign and malignant tumors, including clear-cell renal cell carcinoma (ccRCC). To understand the progression of ccRCC, we generated a novel mouse Vhlh conditional knockout, using Hoxb7-driven Cre that is specific for the collecting ducts and a subset of distal tubules. These mice exhibited wide-spread epithelial disruption and interstitial inflammation as early as 2 months of age with high penetrance. Lesions are cystic, show severe fibrosis and display significant hyperplasia. An abundance of infiltrating macrophages and lymphocytes was detected. Interestingly, the Vhlh mutant lesions could be rescued when Hif-1α, but not Hif-2α, was also knocked out. In addition, administration of a JAK1/2 kinase inhibitor alleviated the Vhlh knockout phenotypes. Taken together, these results suggest that HIF-1α-dependent inflammation and fibrosis may be an early event in the development of ccRCC." @default.
- W2084998185 created "2016-06-24" @default.
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- W2084998185 date "2014-07-14" @default.
- W2084998185 modified "2023-10-17" @default.
- W2084998185 title "Conditional inactivation of the mouse von Hippel–Lindau tumor suppressor gene results in wide-spread hyperplastic, inflammatory and fibrotic lesions in the kidney" @default.
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- W2084998185 doi "https://doi.org/10.1038/onc.2014.197" @default.
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