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Fluvastatin inhibits activation of JAK and STAT proteins in diabetic rat glomeruli and mesangial cells under high glucose conditions

Aim: The aim of the present study was to further elucidate the mechanism of the protective role of fluvastatin on diabetic nephropathy. Methods: Streptozotocin- induced diabetic rats were treated daily with fluvastatin (4 mg/kg body weight) by gavage. The animals were killed 4 weeks later and urine... Full description

Journal Title: Acta pharmacologica Sinica 2007, Vol.28 (12), p.1938-1946
Main Author: SHI, Yong-hong
Other Authors: ZHAO, Song , WANG, Chen , LI, Ying , DUAN, Hui-jun
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Blackwell Publishing
ID: ISSN: 1671-4083
Link: https://www.ncbi.nlm.nih.gov/pubmed/18031608
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title: Fluvastatin inhibits activation of JAK and STAT proteins in diabetic rat glomeruli and mesangial cells under high glucose conditions
format: Article
creator:
  • SHI, Yong-hong
  • ZHAO, Song
  • WANG, Chen
  • LI, Ying
  • DUAN, Hui-jun
subjects:
  • Animals
  • Anticholesteremic Agents - pharmacology
  • Base Sequence
  • Dextrose
  • Diabetes
  • diabetic nephropathy
  • Diabetic Retinopathy - enzymology
  • Diabetic Retinopathy - metabolism
  • DNA Primers
  • Enzyme Activation
  • Fatty Acids, Monounsaturated - pharmacology
  • Fluvastatin
  • Glomerular Mesangium - drug effects
  • Glomerular Mesangium - enzymology
  • Glomerular Mesangium - metabolism
  • Glucose
  • Indoles - pharmacology
  • Janus kinase
  • Janus Kinases - antagonists & inhibitors
  • Janus Kinases - metabolism
  • Male
  • Polypeptides
  • Protein biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • signal transducer and activators of transcription
  • STAT Transcription Factors - antagonists & inhibitors
  • STAT Transcription Factors - metabolism
  • Transforming growth factors
  • 信号转换器
  • 活化剂
  • 糖尿病
ispartof: Acta pharmacologica Sinica, 2007, Vol.28 (12), p.1938-1946
description: Aim: The aim of the present study was to further elucidate the mechanism of the protective role of fluvastatin on diabetic nephropathy. Methods: Streptozotocin- induced diabetic rats were treated daily with fluvastatin (4 mg/kg body weight) by gavage. The animals were killed 4 weeks later and urine and blood samples were collected. The kidney tissues were removed and subjected to the following experiments. Rat glomerular mesangial cells (GMC) were cultured under normal glucose (5.5 mmol/L), high glucose (HG, 30 mmol/L), HG+AG490 (10 μmol/L), or HG with fluvastatin (1 μmol/L). Glomeruli or the GMC lysate was immunoprecipi- tated and/or immunoblotted with antibodies against Janus kinase 2 (JAK2), SH2- domain containing tyrosine phosphatase-1 (SHP-1), phosphospecific SHP-2, and signal transducer and activators of transcription (STAT), respectively. Trans- forming growth factor-13 (TGF-131) mRNA was measured by RT-PCR. The protein synthesis of TGF-β1 and fibronectin in the culture medium of GMC was detected by ELISA. Results: The phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 increased significantly, and SHP-1 phosphorylation was reduced in glom- eruli of diabetic rats. Treatment with fluvastatin reduced phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 in glomeruli of diabetic rats, but it had no effect on the dephosphorylation of SHP-1. The exposure of GMC to 30 mmol/L glucose caused the activation of JAK2, STAT1, STAT3, and SHP-2. It upregulated TGF-131 expression and increased protein synthesis of fibronectin. These high glucose-induced changes were suppressed by fluvastatin, as well as AG490, a JAK2 inhibitor. Conclusion: The regulation of the phosphorylation of JAK/STAT by fluvastatin may be responsible for its renal protective effects on diabetic nephropathy.
language: eng
source:
identifier: ISSN: 1671-4083
fulltext: no_fulltext
issn:
  • 1671-4083
  • 1745-7254
url: Link


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titleFluvastatin inhibits activation of JAK and STAT proteins in diabetic rat glomeruli and mesangial cells under high glucose conditions
creatorSHI, Yong-hong ; ZHAO, Song ; WANG, Chen ; LI, Ying ; DUAN, Hui-jun
creatorcontribSHI, Yong-hong ; ZHAO, Song ; WANG, Chen ; LI, Ying ; DUAN, Hui-jun
descriptionAim: The aim of the present study was to further elucidate the mechanism of the protective role of fluvastatin on diabetic nephropathy. Methods: Streptozotocin- induced diabetic rats were treated daily with fluvastatin (4 mg/kg body weight) by gavage. The animals were killed 4 weeks later and urine and blood samples were collected. The kidney tissues were removed and subjected to the following experiments. Rat glomerular mesangial cells (GMC) were cultured under normal glucose (5.5 mmol/L), high glucose (HG, 30 mmol/L), HG+AG490 (10 μmol/L), or HG with fluvastatin (1 μmol/L). Glomeruli or the GMC lysate was immunoprecipi- tated and/or immunoblotted with antibodies against Janus kinase 2 (JAK2), SH2- domain containing tyrosine phosphatase-1 (SHP-1), phosphospecific SHP-2, and signal transducer and activators of transcription (STAT), respectively. Trans- forming growth factor-13 (TGF-131) mRNA was measured by RT-PCR. The protein synthesis of TGF-β1 and fibronectin in the culture medium of GMC was detected by ELISA. Results: The phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 increased significantly, and SHP-1 phosphorylation was reduced in glom- eruli of diabetic rats. Treatment with fluvastatin reduced phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 in glomeruli of diabetic rats, but it had no effect on the dephosphorylation of SHP-1. The exposure of GMC to 30 mmol/L glucose caused the activation of JAK2, STAT1, STAT3, and SHP-2. It upregulated TGF-131 expression and increased protein synthesis of fibronectin. These high glucose-induced changes were suppressed by fluvastatin, as well as AG490, a JAK2 inhibitor. Conclusion: The regulation of the phosphorylation of JAK/STAT by fluvastatin may be responsible for its renal protective effects on diabetic nephropathy.
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0ISSN: 1671-4083
1EISSN: 1745-7254
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languageeng
publisherUnited States: Blackwell Publishing
subjectAnimals ; Anticholesteremic Agents - pharmacology ; Base Sequence ; Dextrose ; Diabetes ; diabetic nephropathy ; Diabetic Retinopathy - enzymology ; Diabetic Retinopathy - metabolism ; DNA Primers ; Enzyme Activation ; Fatty Acids, Monounsaturated - pharmacology ; Fluvastatin ; Glomerular Mesangium - drug effects ; Glomerular Mesangium - enzymology ; Glomerular Mesangium - metabolism ; Glucose ; Indoles - pharmacology ; Janus kinase ; Janus Kinases - antagonists & inhibitors ; Janus Kinases - metabolism ; Male ; Polypeptides ; Protein biosynthesis ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; signal transducer and activators of transcription ; STAT Transcription Factors - antagonists & inhibitors ; STAT Transcription Factors - metabolism ; Transforming growth factors ; 信号转换器 ; 活化剂 ; 糖尿病
ispartofActa pharmacologica Sinica, 2007, Vol.28 (12), p.1938-1946
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0Fluvastatin inhibits activation of JAK and STAT proteins in diabetic rat glomeruli and mesangial cells under high glucose conditions
1Acta pharmacologica Sinica
addtitleActa Pharmacologica Sinica
descriptionAim: The aim of the present study was to further elucidate the mechanism of the protective role of fluvastatin on diabetic nephropathy. Methods: Streptozotocin- induced diabetic rats were treated daily with fluvastatin (4 mg/kg body weight) by gavage. The animals were killed 4 weeks later and urine and blood samples were collected. The kidney tissues were removed and subjected to the following experiments. Rat glomerular mesangial cells (GMC) were cultured under normal glucose (5.5 mmol/L), high glucose (HG, 30 mmol/L), HG+AG490 (10 μmol/L), or HG with fluvastatin (1 μmol/L). Glomeruli or the GMC lysate was immunoprecipi- tated and/or immunoblotted with antibodies against Janus kinase 2 (JAK2), SH2- domain containing tyrosine phosphatase-1 (SHP-1), phosphospecific SHP-2, and signal transducer and activators of transcription (STAT), respectively. Trans- forming growth factor-13 (TGF-131) mRNA was measured by RT-PCR. The protein synthesis of TGF-β1 and fibronectin in the culture medium of GMC was detected by ELISA. Results: The phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 increased significantly, and SHP-1 phosphorylation was reduced in glom- eruli of diabetic rats. Treatment with fluvastatin reduced phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 in glomeruli of diabetic rats, but it had no effect on the dephosphorylation of SHP-1. The exposure of GMC to 30 mmol/L glucose caused the activation of JAK2, STAT1, STAT3, and SHP-2. It upregulated TGF-131 expression and increased protein synthesis of fibronectin. These high glucose-induced changes were suppressed by fluvastatin, as well as AG490, a JAK2 inhibitor. Conclusion: The regulation of the phosphorylation of JAK/STAT by fluvastatin may be responsible for its renal protective effects on diabetic nephropathy.
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1Anticholesteremic Agents - pharmacology
2Base Sequence
3Dextrose
4Diabetes
5diabetic nephropathy
6Diabetic Retinopathy - enzymology
7Diabetic Retinopathy - metabolism
8DNA Primers
9Enzyme Activation
10Fatty Acids, Monounsaturated - pharmacology
11Fluvastatin
12Glomerular Mesangium - drug effects
13Glomerular Mesangium - enzymology
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15Glucose
16Indoles - pharmacology
17Janus kinase
18Janus Kinases - antagonists & inhibitors
19Janus Kinases - metabolism
20Male
21Polypeptides
22Protein biosynthesis
23Rats
24Rats, Sprague-Dawley
25Reverse Transcriptase Polymerase Chain Reaction
26signal transducer and activators of transcription
27STAT Transcription Factors - antagonists & inhibitors
28STAT Transcription Factors - metabolism
29Transforming growth factors
30信号转换器
31活化剂
32糖尿病
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titleFluvastatin inhibits activation of JAK and STAT proteins in diabetic rat glomeruli and mesangial cells under high glucose conditions
authorSHI, Yong-hong ; ZHAO, Song ; WANG, Chen ; LI, Ying ; DUAN, Hui-jun
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0Animals
1Anticholesteremic Agents - pharmacology
2Base Sequence
3Dextrose
4Diabetes
5diabetic nephropathy
6Diabetic Retinopathy - enzymology
7Diabetic Retinopathy - metabolism
8DNA Primers
9Enzyme Activation
10Fatty Acids, Monounsaturated - pharmacology
11Fluvastatin
12Glomerular Mesangium - drug effects
13Glomerular Mesangium - enzymology
14Glomerular Mesangium - metabolism
15Glucose
16Indoles - pharmacology
17Janus kinase
18Janus Kinases - antagonists & inhibitors
19Janus Kinases - metabolism
20Male
21Polypeptides
22Protein biosynthesis
23Rats
24Rats, Sprague-Dawley
25Reverse Transcriptase Polymerase Chain Reaction
26signal transducer and activators of transcription
27STAT Transcription Factors - antagonists & inhibitors
28STAT Transcription Factors - metabolism
29Transforming growth factors
30信号转换器
31活化剂
32糖尿病
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atitleFluvastatin inhibits activation of JAK and STAT proteins in diabetic rat glomeruli and mesangial cells under high glucose conditions
jtitleActa pharmacologica Sinica
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notes
0fluvastatin; diabetic nephropathy; Januskinase; signal transducer and activators of transcription
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3Januskinase
4R587.1
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631-1347/R
abstractAim: The aim of the present study was to further elucidate the mechanism of the protective role of fluvastatin on diabetic nephropathy. Methods: Streptozotocin- induced diabetic rats were treated daily with fluvastatin (4 mg/kg body weight) by gavage. The animals were killed 4 weeks later and urine and blood samples were collected. The kidney tissues were removed and subjected to the following experiments. Rat glomerular mesangial cells (GMC) were cultured under normal glucose (5.5 mmol/L), high glucose (HG, 30 mmol/L), HG+AG490 (10 μmol/L), or HG with fluvastatin (1 μmol/L). Glomeruli or the GMC lysate was immunoprecipi- tated and/or immunoblotted with antibodies against Janus kinase 2 (JAK2), SH2- domain containing tyrosine phosphatase-1 (SHP-1), phosphospecific SHP-2, and signal transducer and activators of transcription (STAT), respectively. Trans- forming growth factor-13 (TGF-131) mRNA was measured by RT-PCR. The protein synthesis of TGF-β1 and fibronectin in the culture medium of GMC was detected by ELISA. Results: The phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 increased significantly, and SHP-1 phosphorylation was reduced in glom- eruli of diabetic rats. Treatment with fluvastatin reduced phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 in glomeruli of diabetic rats, but it had no effect on the dephosphorylation of SHP-1. The exposure of GMC to 30 mmol/L glucose caused the activation of JAK2, STAT1, STAT3, and SHP-2. It upregulated TGF-131 expression and increased protein synthesis of fibronectin. These high glucose-induced changes were suppressed by fluvastatin, as well as AG490, a JAK2 inhibitor. Conclusion: The regulation of the phosphorylation of JAK/STAT by fluvastatin may be responsible for its renal protective effects on diabetic nephropathy.
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pubBlackwell Publishing
pmid18031608
doi10.1111/j.1745-7254.2007.00653.x
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