부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.bbrc.2005.12.012 Byline: Masayoshi Sakaguchi (a), Motohide Isono (a), Keiji Isshiki (a), Toshiro Sugimoto (a), Daisuke Koya (b), Atsunori Kashiwagi (a) Keywords: Diabetic nephropathy; Renal hypertrophy; Mammalian target of rapamycin; Rapamycin Abstract: Early diabetic nephropathy is characterized by renal hypertrophy that is mainly due to proximal tubular hypertrophy. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase, and its signaling has been reported to regulate protein synthesis and cellular growth, specifically, hypertrophy. Therefore, we examined the effect of mTOR signaling on diabetic renal hypertrophy by using the specific inhibitor for mTOR, rapamycin. Ten days after streptozotocin-induced diabetes, mice showed kidney hypertrophy with increases in the phosphorylation of p70S6kinase and the expression of cyclin kinase inhibitors, p21.sup.Cip1 and p27.sup.Kip1, in the kidneys. The intraperitoneal injection of rapamycin (2mg/kg/day) markedly attenuated the enhanced phosphorylation of p70S6kinase, the increment of cyclin-dependent kinase inhibitors, and renal enlargement without any changes of clinical parameters, including blood glucose, blood pressure, and food intake. Overexpression of a constitutive active form of p70S6kinase resulted in increased cell size of cultured mouse proximal tubule cells; thus, activation of p70S6kinase causes hypertrophy of proximal tubular cells. Our findings suggest that activation of mTOR signaling causes renal hypertrophy at the early stage of diabetes. Author Affiliation: (a) Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan (b) Division of Endocrinology and Metabolism, Kanazawa Medical University, Ishikawa 920-0293, Japan Article History: Received 24 November 2005