Abstract
Transforming growth factor β2 (TGF-β2) is well known to stimulate the expression of pro-fibrotic connective tissue growth factor (CTGF) in several cell types including human mesangial cells. The present study demonstrates that TGF-β2 enhances sphingosine 1-phosphate receptor 5 (S1P5) mRNA and protein expression in a time and concentration dependent manner. Pharmacological and siRNA approaches reveal that this upregulation is mediated via activation of classical TGF-β downstream effectors, Smad and mitogen-activated protein kinases. Most notably, inhibition of Gi with pertussis toxin and downregulation of S1P5 by siRNA block TGF-β2-stimulated upregulation of CTGF, demonstrating that Gi coupled S1P5 is necessary for TGF-β2-triggered expression of CTGF in human mesangial cells. Overall, these findings indicate that TGF-β2 dependent upregulation of S1P5 is required for the induction of pro-fibrotic CTGF by TGF-β. Targeting S1P5 might be an attractive novel approach to treat renal fibrotic diseases.
Original language | English |
---|---|
Pages (from-to) | 519-526 |
Number of pages | 8 |
Journal | Biochimica et Biophysica Acta |
Volume | 1851 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2015 |
Keywords
- Cells, Cultured
- Connective Tissue Growth Factor
- Dose-Response Relationship, Drug
- GTP-Binding Protein alpha Subunits, Gi-Go
- Humans
- Mesangial Cells
- Mitogen-Activated Protein Kinases
- Protein Kinase Inhibitors
- RNA Interference
- RNA, Messenger
- Receptors, Lysosphingolipid
- Smad4 Protein
- Time Factors
- Transfection
- Transforming Growth Factor beta2
- Up-Regulation
- Sphingosine 1-phosphate
- S1P receptor
- Transforming growth factor β2
- Connective tissue growth factor
- Human mesangial cell
- Kidney
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Wünsche, C., Koch, A., Goldschmeding, R., Schwalm, S., Meyer Zu Heringdorf, D., Huwiler, A., & Pfeilschifter, J. (2015). Transforming growth factor β2 (TGF-β2)-induced connective tissue growth factor (CTGF) expression requires sphingosine 1-phosphate receptor 5 (S1P5) in human mesangial cells. Biochimica et Biophysica Acta, 1851(5), 519-526. https://doi.org/10.1016/j.bbalip.2015.01.003
Wünsche, Christin ; Koch, Alexander ; Goldschmeding, Roel et al. / Transforming growth factor β2 (TGF-β2)-induced connective tissue growth factor (CTGF) expression requires sphingosine 1-phosphate receptor 5 (S1P5) in human mesangial cells. In: Biochimica et Biophysica Acta. 2015 ; Vol. 1851, No. 5. pp. 519-526.
@article{00a65da82cc04e918fab485e5809e8d3,
title = "Transforming growth factor β2 (TGF-β2)-induced connective tissue growth factor (CTGF) expression requires sphingosine 1-phosphate receptor 5 (S1P5) in human mesangial cells",
abstract = "Transforming growth factor β2 (TGF-β2) is well known to stimulate the expression of pro-fibrotic connective tissue growth factor (CTGF) in several cell types including human mesangial cells. The present study demonstrates that TGF-β2 enhances sphingosine 1-phosphate receptor 5 (S1P5) mRNA and protein expression in a time and concentration dependent manner. Pharmacological and siRNA approaches reveal that this upregulation is mediated via activation of classical TGF-β downstream effectors, Smad and mitogen-activated protein kinases. Most notably, inhibition of Gi with pertussis toxin and downregulation of S1P5 by siRNA block TGF-β2-stimulated upregulation of CTGF, demonstrating that Gi coupled S1P5 is necessary for TGF-β2-triggered expression of CTGF in human mesangial cells. Overall, these findings indicate that TGF-β2 dependent upregulation of S1P5 is required for the induction of pro-fibrotic CTGF by TGF-β. Targeting S1P5 might be an attractive novel approach to treat renal fibrotic diseases.",
keywords = "Cells, Cultured, Connective Tissue Growth Factor, Dose-Response Relationship, Drug, GTP-Binding Protein alpha Subunits, Gi-Go, Humans, Mesangial Cells, Mitogen-Activated Protein Kinases, Protein Kinase Inhibitors, RNA Interference, RNA, Messenger, Receptors, Lysosphingolipid, Smad4 Protein, Time Factors, Transfection, Transforming Growth Factor beta2, Up-Regulation, Sphingosine 1-phosphate, S1P receptor, Transforming growth factor β2, Connective tissue growth factor, Human mesangial cell, Kidney",
author = "Christin W{\"u}nsche and Alexander Koch and Roel Goldschmeding and Stephanie Schwalm and {Meyer Zu Heringdorf}, Dagmar and Andrea Huwiler and Josef Pfeilschifter",
note = "Copyright {\textcopyright} 2015 Elsevier B.V. All rights reserved.",
year = "2015",
doi = "10.1016/j.bbalip.2015.01.003",
language = "English",
volume = "1851",
pages = "519--526",
journal = "Biochimica et Biophysica Acta",
issn = "0006-3002",
number = "5",
}
Wünsche, C, Koch, A, Goldschmeding, R, Schwalm, S, Meyer Zu Heringdorf, D, Huwiler, A & Pfeilschifter, J 2015, 'Transforming growth factor β2 (TGF-β2)-induced connective tissue growth factor (CTGF) expression requires sphingosine 1-phosphate receptor 5 (S1P5) in human mesangial cells', Biochimica et Biophysica Acta, vol. 1851, no. 5, pp. 519-526. https://doi.org/10.1016/j.bbalip.2015.01.003
Transforming growth factor β2 (TGF-β2)-induced connective tissue growth factor (CTGF) expression requires sphingosine 1-phosphate receptor 5 (S1P5) in human mesangial cells. / Wünsche, Christin; Koch, Alexander; Goldschmeding, Roel et al.
In: Biochimica et Biophysica Acta, Vol. 1851, No. 5, 2015, p. 519-526.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Transforming growth factor β2 (TGF-β2)-induced connective tissue growth factor (CTGF) expression requires sphingosine 1-phosphate receptor 5 (S1P5) in human mesangial cells
AU - Wünsche, Christin
AU - Koch, Alexander
AU - Goldschmeding, Roel
AU - Schwalm, Stephanie
AU - Meyer Zu Heringdorf, Dagmar
AU - Huwiler, Andrea
AU - Pfeilschifter, Josef
N1 - Copyright © 2015 Elsevier B.V. All rights reserved.
PY - 2015
Y1 - 2015
N2 - Transforming growth factor β2 (TGF-β2) is well known to stimulate the expression of pro-fibrotic connective tissue growth factor (CTGF) in several cell types including human mesangial cells. The present study demonstrates that TGF-β2 enhances sphingosine 1-phosphate receptor 5 (S1P5) mRNA and protein expression in a time and concentration dependent manner. Pharmacological and siRNA approaches reveal that this upregulation is mediated via activation of classical TGF-β downstream effectors, Smad and mitogen-activated protein kinases. Most notably, inhibition of Gi with pertussis toxin and downregulation of S1P5 by siRNA block TGF-β2-stimulated upregulation of CTGF, demonstrating that Gi coupled S1P5 is necessary for TGF-β2-triggered expression of CTGF in human mesangial cells. Overall, these findings indicate that TGF-β2 dependent upregulation of S1P5 is required for the induction of pro-fibrotic CTGF by TGF-β. Targeting S1P5 might be an attractive novel approach to treat renal fibrotic diseases.
AB - Transforming growth factor β2 (TGF-β2) is well known to stimulate the expression of pro-fibrotic connective tissue growth factor (CTGF) in several cell types including human mesangial cells. The present study demonstrates that TGF-β2 enhances sphingosine 1-phosphate receptor 5 (S1P5) mRNA and protein expression in a time and concentration dependent manner. Pharmacological and siRNA approaches reveal that this upregulation is mediated via activation of classical TGF-β downstream effectors, Smad and mitogen-activated protein kinases. Most notably, inhibition of Gi with pertussis toxin and downregulation of S1P5 by siRNA block TGF-β2-stimulated upregulation of CTGF, demonstrating that Gi coupled S1P5 is necessary for TGF-β2-triggered expression of CTGF in human mesangial cells. Overall, these findings indicate that TGF-β2 dependent upregulation of S1P5 is required for the induction of pro-fibrotic CTGF by TGF-β. Targeting S1P5 might be an attractive novel approach to treat renal fibrotic diseases.
KW - Cells, Cultured
KW - Connective Tissue Growth Factor
KW - Dose-Response Relationship, Drug
KW - GTP-Binding Protein alpha Subunits, Gi-Go
KW - Humans
KW - Mesangial Cells
KW - Mitogen-Activated Protein Kinases
KW - Protein Kinase Inhibitors
KW - RNA Interference
KW - RNA, Messenger
KW - Receptors, Lysosphingolipid
KW - Smad4 Protein
KW - Time Factors
KW - Transfection
KW - Transforming Growth Factor beta2
KW - Up-Regulation
KW - Sphingosine 1-phosphate
KW - S1P receptor
KW - Transforming growth factor β2
KW - Connective tissue growth factor
KW - Human mesangial cell
KW - Kidney
U2 - 10.1016/j.bbalip.2015.01.003
DO - 10.1016/j.bbalip.2015.01.003
M3 - Article
C2 - 25601519
SN - 0006-3002
VL - 1851
SP - 519
EP - 526
JO - Biochimica et Biophysica Acta
JF - Biochimica et Biophysica Acta
IS - 5
ER -
Wünsche C, Koch A, Goldschmeding R, Schwalm S, Meyer Zu Heringdorf D, Huwiler A et al. Transforming growth factor β2 (TGF-β2)-induced connective tissue growth factor (CTGF) expression requires sphingosine 1-phosphate receptor 5 (S1P5) in human mesangial cells. Biochimica et Biophysica Acta. 2015;1851(5):519-526. doi: 10.1016/j.bbalip.2015.01.003