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논문분류	춘계학술대회 초록집
제목	Restoration of Klotho Ameliorates Glomerular Hypertrophy and Apoptosis in Diabetic Nephropathy
저자	Bo Young Nam, Soon Ha Lee, Hye Young Kang, Ji Sun Pang, Sung Hoon Kim,Mi Jung Lee, Dong Ho Shin, Hyung Jung Oh, Jung Tak Park, Tae-Hyun Yoo,Shin-Wook Kang, Seung Hyeok Han
출판정보	2014; 2014(1):
키워드	klotho, 족세포, 당뇨병성 신병증
초록	Background: Klotho, a known co-receptor for FGF23, has been demonstrated to have a protective role in experimental acute tubule-interstitial injury. However, the effects of klotho on glomeruli are largely unknown in diabetic conditions. Therefore, we aimed to investigate the role of glomerular klotho in diabetic nephropathy (DMN). Methods: Mouse mesangial cells (MMC) and podocytes were treated with either normal glucose (5.6 mM, NG), high glucose (30 mM, HG) or NG+mannitol (24.4 mM, NG+M). Mice were injected either with diluents (n=16, C) or with streptozotocin (50 mg/kg) intraperitoneally (n=16, DM) to induce diabetes. Eight mice from each group were treated daily with 10 ug/kg recombinant klotho (rKL) using osmotic minipumps. Kidneys were collected after 8 weeks. Results: The expressions of klotho mRNA and protein were down-regulated in MMC and podocytes with HG treatment compared to NG or NG+M cells. In parallel, the expressions of p21Cip1, p27Kip1, cleaved caspase-3, and the ratio of Bax/Bcl-2 were significantly increased in HG-treated MMC and podocytes compared to NG or NG+M cells. When MMC and podocytes were treated with rKL, HG-induced p21Cip1, p27Kip1, cleaved caspase-3, and Bax protein expressions were significantly attenuated. In addition, knock down of klotho with siRNA transfection further increased the expression levels of these hypertrophy- and apoptosis- related proteins. In vivo, the expression of klotho was significantly decreased in DM glomeruli compared to C glomeruli at 8 weeks of diabetes. The protein expressions of p21Cip1, p27Kip1, cleaved caspase-3, and the ratio of Bax/Bcl-2 were significantly increased in glomeruli from DM compared to C mice. Treatment with rKL via osmotic minipumps significantly ameliorated the glomerular protein expressions of p21Cip1, p27Kip1, cleaved caspase-3, and Bax in DM compared to DM mice treated with diluent alone. Conclusion: Decreased klotho contributed to the development of cellular hypertrophy and apoptosis in MMC and podocytes under diabetic conditions. Present study revealed that restoration of klotho might be a potential therapeutic target in DMN.
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