Berberine ameliorates renal injury by regulating G proteins-AC- cAMP signaling in diabetic rats with nephropathy
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Diabetic nephropathy (DN) is a progressive kidney disease that is caused by injury to glomerulus and glomerular mesangial cells (MCs) proliferation play a critical role in the pathogenesis of DN. The current studies were undertaken to investigate the protective effects and the possible molecular mechanism of berberine on streptozotocin (STZ)-induced DN rats. Male Wistar rats were randomly assigned to normal control and DN groups of comparable age. Three DN groups received 50, 100 and 200 mg/kg of berberine for 8 weeks via daily intragastrically, respectively. The G proteins-adenylyl cyclase (AC)-cAMP signaling pathway and glomerular MCs proliferation were examined in STZ-induced diabetic rat kidney. Enhanced MCs proliferation and remarkable renal injury were concomitant with activation of Gαi and inhibition of Gαs and cAMP in DN model group. Berberine treatment for 8 weeks abolished the above changes by upregulating the expression of Gαs protein and downregulating the expression of Gαi protein, increasing cAMP level, and inhibiting MCs proliferation compared with model group. Taken together, for the first time, these results demonstrated that berberine can relieve renal injury in DN rats through mediating G proteins-AC-cAMP signaling pathway and inhibiting the abnormal proliferation of MCs by increasing cAMP level, suggesting that berberine could be a potential therapeutic agent for the treatment of DN.
KeywordsBerberine Diabetic nephropathy Cell proliferation G proteins cAMP
- G proteins
Heterotrimeric GTP-binding proteins
Glomerular basement membrane
Adenosine 3-,5- monophosphate
Transforming growth factor-beta1
Connective tissue factor
Fasting blood glucose
This Project was supported by the National Natural Science Foundation of China (Nos. 81073109, 81102864) and Natural Science Foundation of Anhui Province (China, No. 090413106). We would like to extend our appreciation to Wei Wei and the staff at the School of Pharmacy, Anhui College of Traditional Chinese Medicine for their technical support.
Conflict of interest
There are no competing financial interests in relation to the work.
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