Ablation of carbohydrate-responsive element-binding protein improves kidney injury in streptozotocin-induced diabetic
1Department of Nephrology, Jining No. 1, People's Hospital, Jining City, Shandong Province, China. shengguozh@163.com.
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.
Insights
Carbohydrate-responsive element-binding protein (ChREBP) is upregulated in diabetic nephropathy. Inhibiting ChREBP protected mice from kidney damage, reducing albuminuria and inflammation.
Area of Science:
- Metabolic regulation
- Renal pathophysiology
- Molecular mechanisms of disease
Background:
- Carbohydrate-responsive element-binding protein (ChREBP) regulates glucose and lipid metabolism in the liver.
- The role of ChREBP in diabetic nephropathy remains unclear.
Purpose of the Study:
- To investigate the role of ChREBP in diabetic nephropathy.
- To determine if ChREBP ablation protects against kidney damage in a mouse model of diabetes.
Main Methods:
- Streptozotocin (STZ) induced diabetic mouse models.
- Quantification of ChREBP mRNA and protein levels in kidney tissue.
- Assessment of inflammatory and endoplasmic reticulum stress markers.
- Measurement of albuminuria and urine creatinine.
Main Results:
- ChREBP expression and its target genes were upregulated in diabetic nephropathy.
- ChREBP knockout mice showed protection against STZ-induced diabetic nephropathy.
- Reduced albuminuria, inflammation, and glomerular hypertrophy were observed in ChREBP-deficient mice.
Conclusions:
- ChREBP plays a significant role in the development of diabetic nephropathy.
- Ablation or inhibition of ChREBP may offer a therapeutic strategy for diabetic kidney injury.
