Enhanced expression of naofen in kidney of streptozotocin-induced diabetic rats: possible correlation to apoptosis of tubular epithelial cells
Enhanced expression of naofen in kidney of streptozotocin-induced diabetic rats: possible correlation to apoptosis of tubular epithelial cells
复制标题
DOI：
10.1007/s10157-010-0276-1
复制
发表时间：
2010-06-01
影响因子：
2.3
通讯作者：
Ishikawa, Naohisa
中科院分区：
文献类型：
--
作者：
Sato, Yuko;Feng, Guo-Gang;Ishikawa, Naohisa
高血糖/高糖可诱导糖尿病肾脏细胞凋亡，但其机制尚不完全清楚。Naofen是一种志贺毒素(STX)-2相关蛋白。本研究以链脲佐菌素(STZ)诱导的糖尿病大鼠为研究对象，以体外培养的大鼠肾上皮细胞(NRK52E)为研究对象，研究了链脲佐菌素(STZ)诱导的糖尿病大鼠肾功能损害及诺芬参与人胚胎肾细胞凋亡的机制。用原位杂交法研究Naofen基因在糖尿病大鼠肾脏中的表达。用半胱氨酸天冬氨酸氨基转移酶-3活性检测细胞凋亡。糖尿病大鼠肾脏半胱氨酸天冬氨酸氨基转移酶-3活性和Naofen基因表达显著增加。Naofen主要见于近端和远端尿小管。NRK52E细胞在高糖介质中孵育后，其Naofen mRNA表达增加，而IL-1、IL-6和肿瘤坏死因子-α均无此作用。此外，Naofen小干扰RNA(SiRNA)处理NRK52E细胞可抑制高糖诱导的Naofen mRNA表达，并阻断caspase-3活性的升高，提示高血糖可能上调了NAFen的表达，可能与肾小管上皮细胞的凋亡有关，从而参与糖尿病肾病的发生。
Hyperglycemia/high glucose may induce apoptosis in diabetic kidney, but the mechanism is not fully understood. Naofen was found as a Shiga toxin (Stx)-2-related protein. Based on renal dysfunction in infection with Stx-producing Escherichia coli and on participation of naofen in apoptosis of human embryonic kidney cells, the present study was undertaken to investigate the mechanism of renal dysfunction in diabetes mellitus with particular reference to naofen.In in vivo studies utilizing streptozotocin (STZ)-induced diabetic rats, and also in in vitro cultured rat kidney epithelial (NRK52E) cells, naofen messenger RNA (mRNA) and protein expressions were analyzed. Naofen mRNA location in diabetic kidney was studied by in situ hybridization. Apoptosis was assessed by caspase-3 activity assay.Rat diabetic kidney showed significant increases in caspase-3 activities and naofen mRNA. Naofen was mainly observed at both proximal and distal urinary tubules. Incubation of NRK52E cells in high glucose medium resulted in elevated naofen mRNA expression, whereas neither interleukin-1, interleukin-6, nor tumor necrosis factor-alpha elicited such action. Moreover, treatment of NRK52E cells with naofen small interfering RNA (siRNA) inhibited naofen mRNA expression induced by high glucose and blocked the increase in caspase-3 activity.These data suggest that naofen expression may be upregulated by hyperglycemia, with possible correlation to apoptosis of tubular epithelial cells and thereby to diabetic nephropathy.