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JASN:揭示治疗糖尿病肾病的新型靶点

来源:生物谷 2012-10-20 00:14

2012年10月20日 讯 /生物谷BIOON/ --近日,来自日本冈山大学医学研究生院的研究者通过研究发现了一种糖尿病肾病新型的治疗靶点,糖尿病肾病(diabetic nephropathy)是肾功能衰竭的主要原因。相关研究成果刊登于国际著名杂志Journal of the American Society of Nephrology上,这项研究或许为糖尿病患者的肾脏健康带来帮助。

糖尿病肾病,即是在糖尿病患者机体中发生的肾脏疾病和肾脏损伤,随着其病情发展会出现相应的炎症表现,一种特异性的炎性分子-骨桥蛋白,其或许可以作为未来潜在的治疗该疾病的疗法。

这项研究中,研究者通过激活一种受体来阻止引发炎症相关的基因进行表达,这种受体名为x受体LXR,其可以被药物T0901317激活。当肾脏损伤的糖尿病小鼠给予药物T0901317时,其肾脏就会恢复功能,药物T0901317的疗法可以明显降低肾脏中骨桥蛋白和其它炎性分子的表达。实验室肾脏细胞试验表明,高浓度的糖分,就像糖尿病患者的血液一样,可以增加骨桥蛋白的表达,而骨桥蛋白可以被药物T0901317抑制。

研究者Ogawa表示,这些研究成果揭示了LXR激动剂在抑制糖尿病肾病炎性反应中的抑制作用,而且LXR激动剂还可以抑制肾脏病变的发生。(生物谷Bioon.com)

编译自:New Target for Treating Diabetic Kidney Disease, the Leading Cause of Kidney Failure

Activation of Liver X Receptor Inhibits Osteopontin and Ameliorates Diabetic Nephropathy

Hiromi Tachibana*, Daisuke Ogawa*†, Yuichi Matsushita*, Dennis Bruemmer‡, Jun Wada*, Sanae Teshigawara*, Jun Eguchi*, Chikage Sato-Horiguchi*†, Haruhito Adam Uchida*, Kenichi Shikata*§ and Hirofumi Makino*

Osteopontin is a proinflammatory cytokine and monocyte chemoattractant implicated in the pathogenesis of diabetic nephropathy. Synthetic agonists for liver X receptors (LXRs) suppress the expression of proinflammatory genes, including osteopontin, but whether LXR activation modulates diabetic nephropathy is unknown. We administered the LXR agonist T0901317 to mice with streptozotocin-induced diabetes and evaluated its effects on diabetic nephropathy. The LXR agonist decreased urinary albumin excretion without altering blood glucose levels and substantially attenuated macrophage infiltration, mesangial matrix accumulation, and interstitial fibrosis. LXR activation suppressed the gene expression of inflammatory mediators, including osteopontin, in the kidney cortex. In vitro, LXR activation suppressed osteopontin expression in proximal tubular epithelial cells by inhibiting AP-1–dependent transcriptional activation of the osteopontin promoter. Taken together, these results suggest that inhibition of renal osteopontin by LXR agonists may have therapeutic potential for diabetic nephropathy.

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