TY - JOUR
T1 - Extracellular superoxide dismutase ameliorates streptozotocin-induced rat diabetic nephropathy via inhibiting the ROS/ERK1/2 signaling
AU - Kuo, Chia Wen
AU - Shen, Chih Jie
AU - Tung, Yu Tang
AU - Chen, Hsiao Ling
AU - Chen, Yu Hsuan
AU - Chang, Wen Hui
AU - Cheng, Kai Chung
AU - Yang, Shang Hsun
AU - Chen, Chuan Mu
N1 - Funding Information:
Funding: This research was supported by grant NSC-101-2313-B-005-014-MY3 from the National Science Council and was partly supported by the Ministry of Education, Taiwan , under the aiming top university plan ( ATU-103-s0508 ). The funders had no role in this design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/6/22
Y1 - 2015/6/22
N2 - Aim Diabetic nephropathy is the leading cause of end stage renal disease in developed countries throughout the world. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system is the main problem that is responsible for the progression of diabetic kidney disease. In this study, we investigated whether human extracellular superoxide dismutase (hEC-SOD) can prevent diabetic nephropathy in the rat model. Main methods Diabetic nephropathy symptoms were induced by intraperitoneal injection with 60 mg/kg streptozotocin (STZ) in male Sprague-Dawley (SD) rats. After daily supplement of rhEC-SOD (3200 U/kg/day) for 4 weeks, the serum or urine biochemical markers (glucose, creatinine, blood urea nitrogen, triglyceride, hemoglobin A1c, and microalbuminuria), histological changes, gene expressions (phox47, opn, and gapdh), and protein levels (TGF-β, AT1-R, phospho-p42/p44 MAPK, and p42/p44 MAPK) were determined. Key findings Results showed that rhEC-SOD administration could reverse SOD activity measured in kidney and diabetic-associated changes, including the fibrosis change, expression of collagen I, transforming growth factor-beta (TGF-β) and angiotensin II type I receptor (AT1-R), as well as the activation of the intracellular mitogen-activated protein kinase (MAPK) signaling pathway, associating with its inhibition of p42MAPK/p44MAPK (ERK1/2) phosphorylation. Additionally, diabetic nephropathy up-regulated the expression of the phox47 and opn genes, and these changes could also be suppressed. Though the proteinuria did not significantly reduce. Treatment with rhEC-SOD ameliorates STZ-induced diabetic nephropathy, leading to reduced death rates, kidney weight/body weight ratio, fibrosis change, and TGF-β1 expression through the down-regulation of ROS/ERK1/2 signaling pathway. Significance We conclude that rhEC-SOD can act as a therapeutic agent to protect the progression of diabetic nephropathy.
AB - Aim Diabetic nephropathy is the leading cause of end stage renal disease in developed countries throughout the world. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system is the main problem that is responsible for the progression of diabetic kidney disease. In this study, we investigated whether human extracellular superoxide dismutase (hEC-SOD) can prevent diabetic nephropathy in the rat model. Main methods Diabetic nephropathy symptoms were induced by intraperitoneal injection with 60 mg/kg streptozotocin (STZ) in male Sprague-Dawley (SD) rats. After daily supplement of rhEC-SOD (3200 U/kg/day) for 4 weeks, the serum or urine biochemical markers (glucose, creatinine, blood urea nitrogen, triglyceride, hemoglobin A1c, and microalbuminuria), histological changes, gene expressions (phox47, opn, and gapdh), and protein levels (TGF-β, AT1-R, phospho-p42/p44 MAPK, and p42/p44 MAPK) were determined. Key findings Results showed that rhEC-SOD administration could reverse SOD activity measured in kidney and diabetic-associated changes, including the fibrosis change, expression of collagen I, transforming growth factor-beta (TGF-β) and angiotensin II type I receptor (AT1-R), as well as the activation of the intracellular mitogen-activated protein kinase (MAPK) signaling pathway, associating with its inhibition of p42MAPK/p44MAPK (ERK1/2) phosphorylation. Additionally, diabetic nephropathy up-regulated the expression of the phox47 and opn genes, and these changes could also be suppressed. Though the proteinuria did not significantly reduce. Treatment with rhEC-SOD ameliorates STZ-induced diabetic nephropathy, leading to reduced death rates, kidney weight/body weight ratio, fibrosis change, and TGF-β1 expression through the down-regulation of ROS/ERK1/2 signaling pathway. Significance We conclude that rhEC-SOD can act as a therapeutic agent to protect the progression of diabetic nephropathy.
KW - Angiotensin II receptor 1
KW - Diabetic nephropathy
KW - Extracellular superoxide dismutase
KW - Mitogen activated protein kinase
KW - Transforming growth factor-beta
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U2 - 10.1016/j.lfs.2015.04.018
DO - 10.1016/j.lfs.2015.04.018
M3 - Article
C2 - 26006040
AN - SCOPUS:84935002203
SN - 0024-3205
VL - 135
SP - 77
EP - 86
JO - Life Sciences
JF - Life Sciences
ER -
