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Sphingosine kinase 1 regulates differentiation of human and mouse lung fibroblasts mediated by TGF-beta1.
Am J Respir Cell Mol Biol. 2007 Oct; 37(4):395-404.AJ

Abstract

Transforming growth factor beta (TGF-beta) contributes to the progression of pulmonary fibrosis through up-regulation of alpha-smooth muscle actin (alpha-SMA) as lung myofibroblast differentiation. Bioactive sphingosine 1-phosphate (S1P) has been shown to mimic TGF-beta signals; however, the function of S1P in lung fibrotic process has not been well documented. We found, in a mouse model of bleomycin lung fibrosis, that SPHK1 and alpha-SMA were colocalized within lung fibrotic foci and that these expressions were significantly increased in primary cultured fibroblasts. Using human lung fibroblasts WI-38, we explored the rationale of sphingosine kinase (SPHK) with TGF-beta1 stimulation. SPHK inhibitors and small interference RNA (siRNA) targeted SPHK1 decreased alpha-SMA and fibronectin expression up-regulated by TGF-beta1. In the meantime, SPHK1 inhibition did not affect smad2 phosphorylation in response to TGF-beta1. Then we examined whether S1P receptors transactivation may affect TGF-beta signals. siRNA against S1P(2) and S1P(3), but not S1P(1), reduced alpha-SMA expression as well as Y-27632, Rho kinase inhibitor. We also detected activation of Rho GTPase upon stimulation of TGF-beta1 on the cell membrane where S1P(2) or S1P(3) was overexpressed. These data suggested that SPHK1 activation by TGF-beta1 leads to Rho-associated myofibroblasts differentiation mediated by transactivated S1P receptors in the lung fibrogenic process.

Authors+Show Affiliations

Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.No 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

17641298

Citation

Kono, Yuko, et al. "Sphingosine Kinase 1 Regulates Differentiation of Human and Mouse Lung Fibroblasts Mediated By TGF-beta1." American Journal of Respiratory Cell and Molecular Biology, vol. 37, no. 4, 2007, pp. 395-404.
Kono Y, Nishiuma T, Nishimura Y, et al. Sphingosine kinase 1 regulates differentiation of human and mouse lung fibroblasts mediated by TGF-beta1. Am J Respir Cell Mol Biol. 2007;37(4):395-404.
Kono, Y., Nishiuma, T., Nishimura, Y., Kotani, Y., Okada, T., Nakamura, S., & Yokoyama, M. (2007). Sphingosine kinase 1 regulates differentiation of human and mouse lung fibroblasts mediated by TGF-beta1. American Journal of Respiratory Cell and Molecular Biology, 37(4), 395-404.
Kono Y, et al. Sphingosine Kinase 1 Regulates Differentiation of Human and Mouse Lung Fibroblasts Mediated By TGF-beta1. Am J Respir Cell Mol Biol. 2007;37(4):395-404. PubMed PMID: 17641298.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sphingosine kinase 1 regulates differentiation of human and mouse lung fibroblasts mediated by TGF-beta1. AU - Kono,Yuko, AU - Nishiuma,Teruaki, AU - Nishimura,Yoshihiro, AU - Kotani,Yoshikazu, AU - Okada,Taro, AU - Nakamura,Shun-Ichi, AU - Yokoyama,Mitsuhiro, Y1 - 2007/07/19/ PY - 2007/7/21/pubmed PY - 2007/11/1/medline PY - 2007/7/21/entrez SP - 395 EP - 404 JF - American journal of respiratory cell and molecular biology JO - Am J Respir Cell Mol Biol VL - 37 IS - 4 N2 - Transforming growth factor beta (TGF-beta) contributes to the progression of pulmonary fibrosis through up-regulation of alpha-smooth muscle actin (alpha-SMA) as lung myofibroblast differentiation. Bioactive sphingosine 1-phosphate (S1P) has been shown to mimic TGF-beta signals; however, the function of S1P in lung fibrotic process has not been well documented. We found, in a mouse model of bleomycin lung fibrosis, that SPHK1 and alpha-SMA were colocalized within lung fibrotic foci and that these expressions were significantly increased in primary cultured fibroblasts. Using human lung fibroblasts WI-38, we explored the rationale of sphingosine kinase (SPHK) with TGF-beta1 stimulation. SPHK inhibitors and small interference RNA (siRNA) targeted SPHK1 decreased alpha-SMA and fibronectin expression up-regulated by TGF-beta1. In the meantime, SPHK1 inhibition did not affect smad2 phosphorylation in response to TGF-beta1. Then we examined whether S1P receptors transactivation may affect TGF-beta signals. siRNA against S1P(2) and S1P(3), but not S1P(1), reduced alpha-SMA expression as well as Y-27632, Rho kinase inhibitor. We also detected activation of Rho GTPase upon stimulation of TGF-beta1 on the cell membrane where S1P(2) or S1P(3) was overexpressed. These data suggested that SPHK1 activation by TGF-beta1 leads to Rho-associated myofibroblasts differentiation mediated by transactivated S1P receptors in the lung fibrogenic process. SN - 1044-1549 UR - https://www.unboundmedicine.com/medline/citation/17641298/Sphingosine_kinase_1_regulates_differentiation_of_human_and_mouse_lung_fibroblasts_mediated_by_TGF_beta1_ L2 - https://www.atsjournals.org/doi/10.1165/rcmb.2007-0065OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -