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Synergistic Effects of Combining Anti-Midkine and Hepatocyte Growth Factor Therapies Against Diabetic Nephropathy in Rats

Purpose This study aimed to assess whether synergism could be achieved when combining midkine (MK) antisense oligodeoxynucleotides (anti-MK ODN) and recombinant human hepatocyte growth factor (HGF) in diabetic nephropathy (DN) rat models. Methods Rats were randomized into 6 groups: control, DN rats... Full description

Journal Title: The American journal of the medical sciences 2015, Vol.350 (1), p.47-54
Main Author: Ren, Xiaojun, MD
Other Authors: Li, Hui, MD, PhD , Feng, Ping, MD , Wang, Junwei, MD , Meng, Zhaowei, MD, PhD , Zheng, Wei, MD, PhD , Yang, Hui, PhD , Xu, Ke, PhD
Format: Electronic Article Electronic Article
Language: English
Subjects:
Abridged Index Medicus
Albuminuria
Animals
Blood Glucose - drug effects
Blood Urea Nitrogen
Connective tissue growth factor
Creatinine - blood
Cytokines - antagonists & inhibitors
Cytokines - genetics
Diabetic Nephropathies - genetics
Diabetic Nephropathies - metabolism
Diabetic nephropathy
Drug Synergism
Gene Silencing
Hepatocyte growth factor
Hepatocyte Growth Factor - pharmacology
Internal Medicine
Kidney - drug effects
Kidney - metabolism
Midkine
Oligodeoxyribonucleotides, Antisense - pharmacology
Rats
Recombinant Proteins - pharmacology
Synergism
Transforming Growth Factor beta1 - drug effects
Transforming Growth Factor beta1 - metabolism
Transforming growth factor-β1
Publisher: United States: Elsevier Inc
ID: ISSN: 0002-9629
Link: https://www.ncbi.nlm.nih.gov/pubmed/26086153
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recordid: cdi_proquest_miscellaneous_1693187914
title: Synergistic Effects of Combining Anti-Midkine and Hepatocyte Growth Factor Therapies Against Diabetic Nephropathy in Rats
format: Article
creator:
  • Ren, Xiaojun, MD
  • Li, Hui, MD, PhD
  • Feng, Ping, MD
  • Wang, Junwei, MD
  • Meng, Zhaowei, MD, PhD
  • Zheng, Wei, MD, PhD
  • Yang, Hui, PhD
  • Xu, Ke, PhD
subjects:
  • Abridged Index Medicus
  • Albuminuria
  • Animals
  • Blood Glucose - drug effects
  • Blood Urea Nitrogen
  • Connective tissue growth factor
  • Creatinine - blood
  • Cytokines - antagonists & inhibitors
  • Cytokines - genetics
  • Diabetic Nephropathies - genetics
  • Diabetic Nephropathies - metabolism
  • Diabetic nephropathy
  • Drug Synergism
  • Gene Silencing
  • Hepatocyte growth factor
  • Hepatocyte Growth Factor - pharmacology
  • Internal Medicine
  • Kidney - drug effects
  • Kidney - metabolism
  • Midkine
  • Oligodeoxyribonucleotides, Antisense - pharmacology
  • Rats
  • Recombinant Proteins - pharmacology
  • Synergism
  • Transforming Growth Factor beta1 - drug effects
  • Transforming Growth Factor beta1 - metabolism
  • Transforming growth factor-β1
ispartof: The American journal of the medical sciences, 2015, Vol.350 (1), p.47-54
description: Purpose This study aimed to assess whether synergism could be achieved when combining midkine (MK) antisense oligodeoxynucleotides (anti-MK ODN) and recombinant human hepatocyte growth factor (HGF) in diabetic nephropathy (DN) rat models. Methods Rats were randomized into 6 groups: control, DN rats without treatment, DN rats treated with scrambled ODN, DN rats treated with anti-MK ODN, DN rats treated with HGF and DN rats treated with anti-MK ODN plus HGF. DN models were created by intraperitoneal injection of streptozotocin. Two weeks later, treatments commenced. ODN (1 mg/kg) was intravenously injected weekly for 4 weeks. HGF (500 μg/kg) was subcutaneously injected daily for 4 weeks. Eight weeks later, rats were euthanized. Serum and urine parameters, kidney histopathological injury scores, immunohistochemistry and protein expressions were measured. Results Blood glucose, creatinine, blood urea nitrogen and urine albumin were significantly elevated in DN rats. Any single treatment markedly reduced their levels, yet combined treatment decreased them significantly further. Any monotherapy could decrease renal injury score and immunohistochemistry positive percentage, although the most prominent change was displayed in combinational therapy. Western blot showed the expression of MK was significantly elevated in DN rats. Anti-MK ODN suppressed MK significantly. The protein expressions and serum concentrations of transforming growth factor-β1 and connective tissue growth factor between monotherapy and the combined therapy were significant. Conclusions This study demonstrated that combining MK gene suppressing ODN and HGF protein synergistically attenuates renal injury in DN rats. This study may provide a novel avenue for designing future therapeutic regimens against DN.
language: eng
source:
identifier: ISSN: 0002-9629
fulltext: no_fulltext
issn:
  • 0002-9629
  • 1538-2990
url: Link


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titleSynergistic Effects of Combining Anti-Midkine and Hepatocyte Growth Factor Therapies Against Diabetic Nephropathy in Rats
creatorRen, Xiaojun, MD ; Li, Hui, MD, PhD ; Feng, Ping, MD ; Wang, Junwei, MD ; Meng, Zhaowei, MD, PhD ; Zheng, Wei, MD, PhD ; Yang, Hui, PhD ; Xu, Ke, PhD
creatorcontribRen, Xiaojun, MD ; Li, Hui, MD, PhD ; Feng, Ping, MD ; Wang, Junwei, MD ; Meng, Zhaowei, MD, PhD ; Zheng, Wei, MD, PhD ; Yang, Hui, PhD ; Xu, Ke, PhD
descriptionPurpose This study aimed to assess whether synergism could be achieved when combining midkine (MK) antisense oligodeoxynucleotides (anti-MK ODN) and recombinant human hepatocyte growth factor (HGF) in diabetic nephropathy (DN) rat models. Methods Rats were randomized into 6 groups: control, DN rats without treatment, DN rats treated with scrambled ODN, DN rats treated with anti-MK ODN, DN rats treated with HGF and DN rats treated with anti-MK ODN plus HGF. DN models were created by intraperitoneal injection of streptozotocin. Two weeks later, treatments commenced. ODN (1 mg/kg) was intravenously injected weekly for 4 weeks. HGF (500 μg/kg) was subcutaneously injected daily for 4 weeks. Eight weeks later, rats were euthanized. Serum and urine parameters, kidney histopathological injury scores, immunohistochemistry and protein expressions were measured. Results Blood glucose, creatinine, blood urea nitrogen and urine albumin were significantly elevated in DN rats. Any single treatment markedly reduced their levels, yet combined treatment decreased them significantly further. Any monotherapy could decrease renal injury score and immunohistochemistry positive percentage, although the most prominent change was displayed in combinational therapy. Western blot showed the expression of MK was significantly elevated in DN rats. Anti-MK ODN suppressed MK significantly. The protein expressions and serum concentrations of transforming growth factor-β1 and connective tissue growth factor between monotherapy and the combined therapy were significant. Conclusions This study demonstrated that combining MK gene suppressing ODN and HGF protein synergistically attenuates renal injury in DN rats. This study may provide a novel avenue for designing future therapeutic regimens against DN.
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languageeng
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subjectAbridged Index Medicus ; Albuminuria ; Animals ; Blood Glucose - drug effects ; Blood Urea Nitrogen ; Connective tissue growth factor ; Creatinine - blood ; Cytokines - antagonists & inhibitors ; Cytokines - genetics ; Diabetic Nephropathies - genetics ; Diabetic Nephropathies - metabolism ; Diabetic nephropathy ; Drug Synergism ; Gene Silencing ; Hepatocyte growth factor ; Hepatocyte Growth Factor - pharmacology ; Internal Medicine ; Kidney - drug effects ; Kidney - metabolism ; Midkine ; Oligodeoxyribonucleotides, Antisense - pharmacology ; Rats ; Recombinant Proteins - pharmacology ; Synergism ; Transforming Growth Factor beta1 - drug effects ; Transforming Growth Factor beta1 - metabolism ; Transforming growth factor-β1
ispartofThe American journal of the medical sciences, 2015, Vol.350 (1), p.47-54
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6Yang, Hui, PhD
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descriptionPurpose This study aimed to assess whether synergism could be achieved when combining midkine (MK) antisense oligodeoxynucleotides (anti-MK ODN) and recombinant human hepatocyte growth factor (HGF) in diabetic nephropathy (DN) rat models. Methods Rats were randomized into 6 groups: control, DN rats without treatment, DN rats treated with scrambled ODN, DN rats treated with anti-MK ODN, DN rats treated with HGF and DN rats treated with anti-MK ODN plus HGF. DN models were created by intraperitoneal injection of streptozotocin. Two weeks later, treatments commenced. ODN (1 mg/kg) was intravenously injected weekly for 4 weeks. HGF (500 μg/kg) was subcutaneously injected daily for 4 weeks. Eight weeks later, rats were euthanized. Serum and urine parameters, kidney histopathological injury scores, immunohistochemistry and protein expressions were measured. Results Blood glucose, creatinine, blood urea nitrogen and urine albumin were significantly elevated in DN rats. Any single treatment markedly reduced their levels, yet combined treatment decreased them significantly further. Any monotherapy could decrease renal injury score and immunohistochemistry positive percentage, although the most prominent change was displayed in combinational therapy. Western blot showed the expression of MK was significantly elevated in DN rats. Anti-MK ODN suppressed MK significantly. The protein expressions and serum concentrations of transforming growth factor-β1 and connective tissue growth factor between monotherapy and the combined therapy were significant. Conclusions This study demonstrated that combining MK gene suppressing ODN and HGF protein synergistically attenuates renal injury in DN rats. This study may provide a novel avenue for designing future therapeutic regimens against DN.
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0Abridged Index Medicus
1Albuminuria
2Animals
3Blood Glucose - drug effects
4Blood Urea Nitrogen
5Connective tissue growth factor
6Creatinine - blood
7Cytokines - antagonists & inhibitors
8Cytokines - genetics
9Diabetic Nephropathies - genetics
10Diabetic Nephropathies - metabolism
11Diabetic nephropathy
12Drug Synergism
13Gene Silencing
14Hepatocyte growth factor
15Hepatocyte Growth Factor - pharmacology
16Internal Medicine
17Kidney - drug effects
18Kidney - metabolism
19Midkine
20Oligodeoxyribonucleotides, Antisense - pharmacology
21Rats
22Recombinant Proteins - pharmacology
23Synergism
24Transforming Growth Factor beta1 - drug effects
25Transforming Growth Factor beta1 - metabolism
26Transforming growth factor-β1
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titleSynergistic Effects of Combining Anti-Midkine and Hepatocyte Growth Factor Therapies Against Diabetic Nephropathy in Rats
authorRen, Xiaojun, MD ; Li, Hui, MD, PhD ; Feng, Ping, MD ; Wang, Junwei, MD ; Meng, Zhaowei, MD, PhD ; Zheng, Wei, MD, PhD ; Yang, Hui, PhD ; Xu, Ke, PhD
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1Albuminuria
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3Blood Glucose - drug effects
4Blood Urea Nitrogen
5Connective tissue growth factor
6Creatinine - blood
7Cytokines - antagonists & inhibitors
8Cytokines - genetics
9Diabetic Nephropathies - genetics
10Diabetic Nephropathies - metabolism
11Diabetic nephropathy
12Drug Synergism
13Gene Silencing
14Hepatocyte growth factor
15Hepatocyte Growth Factor - pharmacology
16Internal Medicine
17Kidney - drug effects
18Kidney - metabolism
19Midkine
20Oligodeoxyribonucleotides, Antisense - pharmacology
21Rats
22Recombinant Proteins - pharmacology
23Synergism
24Transforming Growth Factor beta1 - drug effects
25Transforming Growth Factor beta1 - metabolism
26Transforming growth factor-β1
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abstractPurpose This study aimed to assess whether synergism could be achieved when combining midkine (MK) antisense oligodeoxynucleotides (anti-MK ODN) and recombinant human hepatocyte growth factor (HGF) in diabetic nephropathy (DN) rat models. Methods Rats were randomized into 6 groups: control, DN rats without treatment, DN rats treated with scrambled ODN, DN rats treated with anti-MK ODN, DN rats treated with HGF and DN rats treated with anti-MK ODN plus HGF. DN models were created by intraperitoneal injection of streptozotocin. Two weeks later, treatments commenced. ODN (1 mg/kg) was intravenously injected weekly for 4 weeks. HGF (500 μg/kg) was subcutaneously injected daily for 4 weeks. Eight weeks later, rats were euthanized. Serum and urine parameters, kidney histopathological injury scores, immunohistochemistry and protein expressions were measured. Results Blood glucose, creatinine, blood urea nitrogen and urine albumin were significantly elevated in DN rats. Any single treatment markedly reduced their levels, yet combined treatment decreased them significantly further. Any monotherapy could decrease renal injury score and immunohistochemistry positive percentage, although the most prominent change was displayed in combinational therapy. Western blot showed the expression of MK was significantly elevated in DN rats. Anti-MK ODN suppressed MK significantly. The protein expressions and serum concentrations of transforming growth factor-β1 and connective tissue growth factor between monotherapy and the combined therapy were significant. Conclusions This study demonstrated that combining MK gene suppressing ODN and HGF protein synergistically attenuates renal injury in DN rats. This study may provide a novel avenue for designing future therapeutic regimens against DN.
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pubElsevier Inc
pmid26086153
doi10.1097/MAJ.0000000000000510