Decrease of Klotho in the Kidney of Streptozotocin-Induced Diabetic Rats

Meng-Fu Cheng,Li-Jen Chen,Juei-Tang Cheng

doi:10.1155/2010/513853

Abstract

The klotho gene is expressed in a limited number of tissues, most notably in distal convoluted tubules in the kidney and choroid plexus in the brain. A previous study suggested that Klotho increases resistance to oxidative stress. However, changes of Klotho expression in high glucose-induced oxidative stress remain unclear. In the present study, we used streptozotocin-induced diabetic rats (STZ rats) to examine the effects of insulin, phloridzin or antioxidant, tiron on diabetic nephropathy. Both insulin and phloridzin reversed the lower Klotho expression levels in kidneys of STZ rats by the correction of hyperglycemia. Also, renal functions were improved by these treatments. In addition to the improvement of renal functions, the decrease of Klotho expression in kidney of STZ rats was also reversed by tiron without changing blood glucose levels. The reduction of oxidative stress induced by high glucose can be considered for this action of tiron. This view was further confirmed in vitro using high glucose-exposed Madin-Darby canine kidney (MDCK) epithelial cells. Thus, we suggest that decrease of oxidative stress is not only responsible for the improvement of renal function but also for the recovery of Klotho expression in kidney of STZ rats.

Highlights

The Klotho gene, named from a Greek goddess who spins the thread of life, was identified in 1997 as a gene mutated in the Klotho mouse, which exhibited multiple disorders resembling human premature-aging syndrome [1]
After 9 weeks of diabetes induction, the serum levels of glucose, blood urea nitrogen (BUN), and creatinine in STZ rats were markedly higher than in age-matched normal rats (Table 1); Actin cells. (a) Western blot analysis of Klotho expression in normal glucose (5 mmol/L) medium in Madin-Darby canine kidney (MDCK) cells treated with H2O2
Western blot analysis was used to detect Klotho (b) expression in MDCK cells cultured with normal glucose (5 mmol/L; control) or high glucose (40 mmol/L glucose; HG) medium with or without tiron (10 mmol/L) treatment

Summary

Introduction

The Klotho gene, named from a Greek goddess who spins the thread of life, was identified in 1997 as a gene mutated in the Klotho mouse, which exhibited multiple disorders resembling human premature-aging syndrome [1] It is expressed in a limited numbers of tissues, most notably in distal convoluted tubules of kidney and choroid plexus of brain [1]. A previous study showed that overexpression of Klotho in a mouse model of glomerulonephritis restored mitochondrial function and suppressed mitochondrial DNA damage in kidney [2]. It suppressed the accelerated cellular senescence and apoptosis induced by glomerulonephritis, resulting in preservation of renal function and improvement of survival [2]. The effect of ROS on changes of Klotho expression in diabetic nephropathy is unknown

Methods

Results

Conclusion