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Different distribution and expression of mammalian target of rapamycin complex in the kidney of diabetic nephropathy mice
ZHAO Hong JI Qian-qian LI Yong-xia DUAN Qiu-hong YAO Li-jun*
Acta Anatomica Sinica ›› 2014, Vol. 45 ›› Issue (4) : 555-560.
Different distribution and expression of mammalian target of rapamycin complex in the kidney of diabetic nephropathy mice
Objective To investigate the different distribution and expression of mammalian target of rapamycin complex (mTORC) in the kidney of diabetic nephropathy (DN) mice. Methods Fourteen eight-week-old male C57BL/6 mice were assigned to 2 groups: the control group (n=7) and the streptozotocin (STZ)-induced DN group (n=7). Blood and urinary variables including glucose, albumin, creatinine and albumin/creatinine ratio were assessed 2 weeks after STZ injection. Hematoxylin-eosin staining was performed for renal pathological analyses. The distributions of mTOR, phosph-ser2448-mTOR(p-mTOR), mTORC1(Raptor), mTORC2(Rictor) and phosph-ser240/244-S6K1 (p-S6K1) were determined by immunofluorescence. The expression levels of mTOR, p-mTOR, mTORC1(Raptor), mTORC2(Rictor), S6K1 and p-S6K1 were detected by Western blotting. Results Two weeks after STZ injection, the diabetic mice developed albuminuria (P<0.01) and renal hypertrophy (P<0.05). The immunofluorescence positive staining for mTOR, Raptor, and Rictor was distributed in the epithelial cells of proximal tubules, glomerular mesangium and capillary loops as well as the medullary collecting ducts of the control mouse kidney. These positive signals increased in the DN mouse kidney (P<0.05). However, pS6K1 was not detected in the inner medulla of control mouse and p-mTOR was not found in the glomeruli of both control and DN mice. Conclusion mTORC is widely expessed in the mouse kidney and participates in the development of DN, whereas the 2448 serine phosphorylation of mTOR may be not implicated in the hyperglycemia mediated glomerular injury.
Mammaliam target of rapamycin / Diabetic nephropathy / Rictor / Raptor / Immunofluorescence / Western blotting / Mouse
[1]Lloberas N, Cruzado JM, Franquesa M, et al. Mammalian target of rapamycin pathway blockade slows progression of diabetic kidney disease in rats [J]. J Am Soc Nephrol, 2006, 17(5):1395-1404.
[2]Flaquer M, Lloberas N, Franquesa M, et al. The combination of sirolimus and rosiglitazone produces a renoprotective effect on diabetic kidney disease in rats [J]. Life Sci, 2010, 87(5-6):147-153.
[3]Mori H, Inoki K, Masutani K, et al. The mTOR pathway is highly activated in diabetic nephropathy and rapamycin has a strong therapeutic potential [J]. Biochem Biophys Res Commun, 2009, 384(4):471-475.
[4]Huang J, Manning BD. A complex interplay between Akt, TSC2 and the two mTOR complexes [J]. Biochem Soc Trans, 2009, 37(Pt 1):217-222.
[5]Laplante M, Sabatini DM. mTOR signaling at a glance [J]. J Cell Sci, 2009, 122(20):3589-3594.
[6]Yao LJ, Wang JQ, Zhao H, et al. Effect of telmisartan on expression of protein kinase C-alpha in kidneys of diabetic mice [J]. Acta Pharmacol Sin, 2007, 28(6):829-838.
[7]Yao LJ, Wang JQ, Deng AG, et al.Protein kinase C-betaI, betaII in mouse diabetic nephropathy kidney and its relation to nephroprotective actions of the angiotensin receptor blocker telmisartan[J].National Medical Journal of China, 2007,87(28):1991-1995.(in Chinese)
姚丽君,王剑清,邓安国,等.蛋白激酶C –βI,βⅡ在糖尿病肾病小鼠肾组织中的分布、表达及替米沙坦对其影响[J].中华医学杂志,2007,87(28):1991-1995.
[8]Duan LJ, Wang GP, Yang XG, et al. mTOR signaling pathway regulates growth of eight liver cell types during rat liver regeneration [J]. Acta Anatomica Sinica, 2012, 43(2): 205-213. (in Chinese)
段丽娟,王改平,杨献光,等.哺乳动物雷帕霉素靶蛋白信号通路相关基因对大鼠再生肝8种细胞生长过程的调节作用[J]. 解剖学报,2012,43(2): 205-213.
[9]Lieberthal W, Levine JS. Mammalian target of rapamycin and the kidney. II. Pathophysiology and therapeutic implications [J]. Am J Physiol Renal Physiol, 2012, 303(2):F180-F191.
[10]Laplante M, Sabatini DM. mTOR signaling in growth control and disease [J]. Cell, 2012, 149(2): 274-293.
[11]Sakaguchi M,Isono M,Isshiki K,et al.Inhibition of mTOR signaling with rapamycin attenuates renal hypertrophy in the early diabetic mice [J].Bioehem Biophys Res Cornmnn, 2006, 340(1): 296-301.
[12]Lieberthal W, Levine JS. Mammalian target of rapamycin and the kidney. I. The signaling pathway [J]. Am J Physiol Renal Physiol, 2012, 303(1):F1-F10.
[13]G?del M, Hartleben B, Herbach N, et al. Role of mTOR in podocyte function and diabetic nephropathy in humans and mice [J]. J Clin Invest, 2011, 121(6):2197-2209.
[14]Balsara BR, Pei J, Mitsuuchi Y, et al. Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions [J]. Carcinogenesis, 2004, 25(11):2053-2059. [15]Zhou X, Tan M, Stone Hawthorne V, et al. Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers [J]. Clin Cancer Res, 2004, 10(20):6779-6788.
[16]Choe G, Horvath S, Cloughesy TF, et al. Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo [J]. Cancer Res, 2003, 63(11):2742-2746.
[17]Altomare DA, Wang HQ, Skele KL, et al. AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth [J]. Oncogene, 2004, 23(34):5853-5857.
[18]Bilgen Ekim, Brian Magnuson, Hugo A, et al. mTOR kinase domain phosphorylation promotes mTORC1 signaling, cell growth, and cell cycle progression [J]. Mol Cell Biol, 2011, 31(14): 2787-2801.
[19]Chen Z, Dong H, Jia C, et al. Activation of mTORC1 in collecting ducts causes hyperkalemia [J]. J Am Soc Nephrol, 2013, 24(11): Epub ahead of print.
[20]Mori H, Inoki K, Masutani K, et al. The mTOR pathway is highly activated in diabetic nephropathy and rapamycin has a strong therapeutic potential [J]. Biochem Biophys Res Commun, 2009, 384(4):471-475.
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