Ablation of carbohydrate-responsive element-binding protein improves kidney injury in streptozotocin-induced diabetic mice

W. Zhang, X. Li, S.-G. Zhou

Department of Nephrology, Jining No. 1, People’s Hospital, Jining City, Shandong Province, China. shengguozh@163.com

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• Metabolism

OBJECTIVE: Carbohydrate-responsive element-binding protein (ChREBP) has been reported to regulate glucose and lipids metabolism in the liver. However, its role in the complicated pathophysiology of diabetic nephropathy is not understood.

MATERIALS AND METHODS: C57BL/6 mice treated with streptozotocin (STZ) or vehicle control to induce diabetic models. The mRNA and protein levels of ChREBP in kidneys of control and diabetic mice were determined by real-time PCR or Western Blot, respectively. The expression of inflammatory and endoplasmic reticulum stress markers in ChREBP deficient or Wild-type mice was also determined by real-time PCR or Western Blot. Urine was collected over 16 hours on the day prior to sacrifice, and albuminuria and urine creatinine were determined by Elisa or Creatinine Assay Kit.

RESULTS: We found that expression of ChREBP and its downstream target genes were up-regulated in C57BL/6 mice with diabetic nephropathy. Subsequently, we demonstrated that ChREBP knockout mice were protected against the development of diabetic nephropathy induced by streptozotocin (STZ), showing less albuminuria, inflammation and glomerular hypertrophy as compared to diabetic wild-type mice. Reduced expression of inflammatory and endoplasmic reticulum stress markers were also observed in ChREBP deficient mice.

CONCLUSIONS: Our data indicate that ablation or inhibition of ChREBP might improve kidney injury in streptozotocin-induced diabetic animals.

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