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; 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

[img] Text
Transforming growth factor β2 (TGF-β2)-induced connective tissue.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (1MB) | Request a copy

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 and 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:

29 May 2017 17:41

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

Actions (login required)

Edit item Edit item
Provide Feedback