mTOR信号转导与肾脏损伤解析.pptVIP

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2016-10-26 发布于湖北
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mTOR信号转导与肾脏损伤解析.ppt

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Rapamycin ameliorates kidney ?brosis in Fibroblast-Tsc1-/- mice Summary (2) TSC/Rheb/mTORC1 signaling activation promotes fibroblast activation and kidney interstitial ?brosis. Rictor/mTORC2 in tubular cell survival and AKIRheb/mTORC1 in fibroblast activation and kidney fibrosisRictor/mTORC2 in fibroblast activation and kidney fibrosis Activation of mTORC2 signaling in the fibroblasts from the fibrotic kidneys Knocking down Rictor expression blocks TGFβ1-induced NRK-49F cell activation Creating mice with Specific deletion of Rictor in ?broblast Specific deletion of Rictor in ?broblast ameliorates UUO nephropathy in mice Summary (3) Rictor/mTORC2 regulates ?broblast activation and kidney fibrosis in mice with UUO nephropathy. Conclusion Rictor/MtorC2 protects against cisplatin-induced tubular cell apoptosis and AKI; Both TSC/Rheb/mTORC1 and Rictor/mTORC2 signalings play important roles in promoting fibroblast activation and kidney fibrosis. 致谢科技部973项目（2012CB51761）国家自然科学基金（面上项目,）江苏省特聘教授计划启动经费杨俊伟教授何伟春副教授江蕾博士曾智凤博士后徐卓博士生峁俊花硕士生李建中硕士生任加法硕士生谢谢 mTOR信号转导与肾脏损伤 The structure and discovery of rapamycin Rapamycins are macrocyclic lactones that possess immunosuppressive, antifungal and antitumor properties Rapa Nui Structure The key events for rapamycin 1970 Rapamycin-producing Streptomyces hygroscopicus taken from Rapa Nui 1975 Purification of rapamycin and identification of fungicidal activity 1977 Immunosuppressive activity discovered 1984 Antitumour activity discovered 1995 Identification of the target of rapamycin in mammalian (mTOR) 1999 Approved by US FDA for use in preventing host-rejection 2003 Approved by FDA for use in drug-eluting stents 2007 Approved by FDA for treatment of renal-cell carcinoma 2008 Approved by FDA for treatment of mantle cell lymphoma 2010 Approved by FDA for treatment of tuberous sclerosis 2011 Approved by FDA for treatment of pancreatic cancer 2013 Crystal structure of mTOR di