Nature Publishing Group;London: Springer Science and Business Media LLC
摘要:
摘要： 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-1 α, but not Hif-2 α, 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. 其他題名： Oncogene 出版者： London: Springer Science and Business Media LLC 出版日期： 2015-05-14 出處： Oncogene, 2015-05, Vol.34 (20), p.2631-2639 資源來源： EBSCOhost Academic Search Premier 版權： Macmillan Publishers Limited 2015 版權： COPYRIGHT 2015 Nature Publishing Group 版權： Copyright Nature Publishing Group May 14, 2015 版權： Macmillan Publishers Limited 2015. 識別號： ISSN: 0950-9232 識別號： ISSN: 1476-5594 識別號： EISSN: 1476-5594 識別號： DOI: 10.1038/onc.2014.197 識別號： PMID: 25023703 識別號： CODEN: ONCNES
