Wünsche, Christin; Koch, Alexander; Goldschmeding, Roel; Schwalm, Stephanie; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef (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 (BBA) - molecular and cell biology of lipids, 1851(5), pp. 519-526. Elsevier 10.1016/j.bbalip.2015.01.003
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology |
UniBE Contributor: |
Wünsche, Christin, Schwalm, Stephanie, Huwiler, Andrea |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1388-1981 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Debora Scherrer |
Date Deposited: |
23 Feb 2016 15:30 |
Last Modified: |
05 Dec 2022 14:52 |
Publisher DOI: |
10.1016/j.bbalip.2015.01.003 |
PubMed ID: |
25601519 |
Uncontrolled Keywords: |
Connective tissue growth factor; Human mesangial cell; Kidney; S1P receptor; Sphingosine 1-phosphate; Transforming growth factor β2 |
BORIS DOI: |
10.7892/boris.76767 |
URI: |
https://boris.unibe.ch/id/eprint/76767 |
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