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Sphingosine-1-phosphate is increased in patients with idiopathic pulmonary fibrosis and mediates epithelial to mesenchymal transition.
Thorax. 2012 Feb; 67(2):147-56.T

Abstract

BACKGROUND

Idiopathic pulmonary fibrosis (IPF) is characterised by the aberrant epithelial to mesenchymal transition (EMT) and myofibroblast accumulation. Sphingosine-1-phosphate (S1P) and sphingosine kinase 1 (SPHK1) have been implicated in lung myofibroblast transition, but their role in EMT and their expression in patients with IPF is unknown.

METHODS AND RESULTS

S1P levels were measured in serum (n=27) and bronchoalveolar lavage (BAL; n=15) from patients with IPF and controls (n=30 for serum and n=15 for BAL studies). SPHK1 expression was measured in lung tissue from patients with IPF (n=12) and controls (n=15). Alveolar type II transformation into mesenchymal cells was studied in response to S1P (10(-9)-10(-5) M). The median (IQR) of S1P serum levels was increased in patients with IPF (1.4 (0.4) μM) versus controls (1 (0.26) μM; p<0.0001). BAL S1P levels were increased in patients with IPF (1.12 (0.53) μM) versus controls (0.2 (0.5); p<0.0001) and correlated with diffusion capacity of the lung for carbon monoxide, forced expiratory volume in 1 s and forced vital capacity (Spearman's r=-0.87, -0.72 and -0.68, respectively) in patients with IPF. SPHK1 was upregulated in lung tissue from patients with IPF and correlated with α-smooth muscle actin, vimentin and collagen type I (Spearman's r=0.82, 0.85 and 0.72, respectively). S1P induced EMT in alveolar type II cells by interacting with S1P(2) and S1P(3), as well as by the activation of p-Smad3, RhoA-GTP, oxidative stress and transforming growth factor-β1 (TGF-β1) release. Furthermore, TGF-β1-induced EMT was partially conducted by the S1P/SPHK1 activation, suggesting crosstalk between TGF-β1 and the S1P/SPHK1 axis.

CONCLUSIONS

S1P is elevated in patients with IPF, correlates with the lung function and mediates EMT.

Authors+Show Affiliations

Research foundation, University General Hospital Consortium, Valencia, Spain. xmilara@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22106015

Citation

Milara, Javier, et al. "Sphingosine-1-phosphate Is Increased in Patients With Idiopathic Pulmonary Fibrosis and Mediates Epithelial to Mesenchymal Transition." Thorax, vol. 67, no. 2, 2012, pp. 147-56.
Milara J, Navarro R, Juan G, et al. Sphingosine-1-phosphate is increased in patients with idiopathic pulmonary fibrosis and mediates epithelial to mesenchymal transition. Thorax. 2012;67(2):147-56.
Milara, J., Navarro, R., Juan, G., Peiró, T., Serrano, A., Ramón, M., Morcillo, E., & Cortijo, J. (2012). Sphingosine-1-phosphate is increased in patients with idiopathic pulmonary fibrosis and mediates epithelial to mesenchymal transition. Thorax, 67(2), 147-56. https://doi.org/10.1136/thoraxjnl-2011-200026
Milara J, et al. Sphingosine-1-phosphate Is Increased in Patients With Idiopathic Pulmonary Fibrosis and Mediates Epithelial to Mesenchymal Transition. Thorax. 2012;67(2):147-56. PubMed PMID: 22106015.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sphingosine-1-phosphate is increased in patients with idiopathic pulmonary fibrosis and mediates epithelial to mesenchymal transition. AU - Milara,Javier, AU - Navarro,Rafael, AU - Juan,Gustavo, AU - Peiró,Teresa, AU - Serrano,Adela, AU - Ramón,Mercedes, AU - Morcillo,Esteban, AU - Cortijo,Julio, Y1 - 2011/11/21/ PY - 2011/11/23/entrez PY - 2011/11/23/pubmed PY - 2012/3/22/medline SP - 147 EP - 56 JF - Thorax JO - Thorax VL - 67 IS - 2 N2 - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by the aberrant epithelial to mesenchymal transition (EMT) and myofibroblast accumulation. Sphingosine-1-phosphate (S1P) and sphingosine kinase 1 (SPHK1) have been implicated in lung myofibroblast transition, but their role in EMT and their expression in patients with IPF is unknown. METHODS AND RESULTS: S1P levels were measured in serum (n=27) and bronchoalveolar lavage (BAL; n=15) from patients with IPF and controls (n=30 for serum and n=15 for BAL studies). SPHK1 expression was measured in lung tissue from patients with IPF (n=12) and controls (n=15). Alveolar type II transformation into mesenchymal cells was studied in response to S1P (10(-9)-10(-5) M). The median (IQR) of S1P serum levels was increased in patients with IPF (1.4 (0.4) μM) versus controls (1 (0.26) μM; p<0.0001). BAL S1P levels were increased in patients with IPF (1.12 (0.53) μM) versus controls (0.2 (0.5); p<0.0001) and correlated with diffusion capacity of the lung for carbon monoxide, forced expiratory volume in 1 s and forced vital capacity (Spearman's r=-0.87, -0.72 and -0.68, respectively) in patients with IPF. SPHK1 was upregulated in lung tissue from patients with IPF and correlated with α-smooth muscle actin, vimentin and collagen type I (Spearman's r=0.82, 0.85 and 0.72, respectively). S1P induced EMT in alveolar type II cells by interacting with S1P(2) and S1P(3), as well as by the activation of p-Smad3, RhoA-GTP, oxidative stress and transforming growth factor-β1 (TGF-β1) release. Furthermore, TGF-β1-induced EMT was partially conducted by the S1P/SPHK1 activation, suggesting crosstalk between TGF-β1 and the S1P/SPHK1 axis. CONCLUSIONS: S1P is elevated in patients with IPF, correlates with the lung function and mediates EMT. SN - 1468-3296 UR - https://www.unboundmedicine.com/medline/citation/22106015/Sphingosine_1_phosphate_is_increased_in_patients_with_idiopathic_pulmonary_fibrosis_and_mediates_epithelial_to_mesenchymal_transition_ L2 - http://thorax.bmj.com/cgi/pmidlookup?view=long&amp;pmid=22106015 DB - PRIME DP - Unbound Medicine ER -