Downregulation of klotho gene expression in streptozotocin‐induced diabetic rats

Abstract

Objective: The expression of klotho, which may function as an anti‐aging hormone, is most abundant in the kidney. We have investigated the regulation of klotho expression in the kidneys of diabetic rats.Methods: Diabetes was induced by a single i.v. injection of streptozotocin (STZ) at a dose of 60 mg/kg. Renal klotho expression was investigated 8 weeks post‐STZ injection. Some rats were given losartan or deferoxamine from 5 weeks post‐STZ injection until sacrifice. Klotho expression was examined by Western blot analysis and quantitative reverse transcription‐polymerase chain reaction.Results: Expression of Klotho protein was reduced by approximately a third in the kidneys of diabetic rats compared to that of the untreated control rats. This downregulation was suppressed by either losartan or deferoxamine; these drugs also decreased the albuminuria. Histological study showed that, in the kidneys of the STZ‐induced diabetic rats, mRNA expression of klotho, albeit less intense than in the untreated control, was observed in the tubular epithelial cells, and was co‐localized with heme oxygenase‐1, an oxidative stress‐sensitive gene.Conclusion: Expression of klotho was downregulated in the kidneys of diabetic rats. An activation of the renin‐angiotensin system, altered iron homeostasis, and presumably enhanced oxidative stress, may play a role in this phenomenon.