Extracellular superoxide dismutase ameliorates streptozotocin-induced rat diabetic nephropathy via inhibiting the ROS/ERK1/2 signaling

Chia Wen Kuo, Chih Jie Shen, Yu Tang Tung, Hsiao Ling Chen, Yu Hsuan Chen, Wen Hui Chang, Kai Chung Cheng, Shang Hsun Yang, Chuan Mu Chen

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)77-86
Number of pages10
JournalLife Sciences
Volume135
DOIs
Publication statusPublished - Jun 22 2015
Externally publishedYes

Fingerprint

Diabetic Nephropathies
Streptozocin
Mitogen-Activated Protein Kinases
Transforming Growth Factor beta
Superoxide Dismutase
Rats
Reactive Oxygen Species
Transforming Growth Factor beta1
Phosphorylation
Mitogen-Activated Protein Kinase 1
Gene expression
Angiotensin II
Urea
Creatinine
Hemoglobins
Triglycerides
Blood
Nitrogen
Collagen
Antioxidants

Keywords

  • Angiotensin II receptor 1
  • Diabetic nephropathy
  • Extracellular superoxide dismutase
  • Mitogen activated protein kinase
  • Transforming growth factor-beta

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Extracellular superoxide dismutase ameliorates streptozotocin-induced rat diabetic nephropathy via inhibiting the ROS/ERK1/2 signaling. / Kuo, Chia Wen; Shen, Chih Jie; Tung, Yu Tang; Chen, Hsiao Ling; Chen, Yu Hsuan; Chang, Wen Hui; Cheng, Kai Chung; Yang, Shang Hsun; Chen, Chuan Mu.

In: Life Sciences, Vol. 135, 22.06.2015, p. 77-86.

Research output: Contribution to journalArticle

Kuo, Chia Wen ; Shen, Chih Jie ; Tung, Yu Tang ; Chen, Hsiao Ling ; Chen, Yu Hsuan ; Chang, Wen Hui ; Cheng, Kai Chung ; Yang, Shang Hsun ; Chen, Chuan Mu. / Extracellular superoxide dismutase ameliorates streptozotocin-induced rat diabetic nephropathy via inhibiting the ROS/ERK1/2 signaling. In: Life Sciences. 2015 ; Vol. 135. pp. 77-86.
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AU - Chen, Hsiao Ling

AU - Chen, Yu Hsuan

AU - Chang, Wen Hui

AU - Cheng, Kai Chung

AU - Yang, Shang Hsun

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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.

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KW - Mitogen activated protein kinase

KW - Transforming growth factor-beta

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