دورية أكاديمية
Sphingosine Kinase 1/S1P Signaling Contributes to Pulmonary Fibrosis by Activating Hippo/YAP Pathway and Mitochondrial Reactive Oxygen Species in Lung Fibroblasts
| العنوان: | Sphingosine Kinase 1/S1P Signaling Contributes to Pulmonary Fibrosis by Activating Hippo/YAP Pathway and Mitochondrial Reactive Oxygen Species in Lung Fibroblasts |
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| المؤلفون: | Long Shuang Huang, Tara Sudhadevi, Panfeng Fu, Prasanth-Kumar Punathil-Kannan, David Lenin Ebenezer, Ramaswamy Ramchandran, Vijay Putherickal, Paul Cheresh, Guofei Zhou, Alison W. Ha, Anantha Harijith, David W. Kamp, Viswanathan Natarajan |
| المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 6, p 2064 (2020) |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | lung fibroblast, yap signaling, sphk1, s1p, tgf-β, pulmonary fibrosis, blm, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | The sphingosine kinase 1 (SPHK1)/sphingosine−1−phosphate (S1P) signaling axis is emerging as a key player in the development of idiopathic pulmonary fibrosis (IPF) and bleomycin (BLM)-induced lung fibrosis in mice. Recent evidence implicates the involvement of the Hippo/Yes-associated protein (YAP) 1 pathway in lung diseases, including IPF, but its plausible link to the SPHK1/S1P signaling pathway is unclear. Herein, we demonstrate the increased co-localization of YAP1 with the fibroblast marker FSP1 in the lung fibroblasts of BLM-challenged mice, and the genetic deletion of Sphk1 in mouse lung fibroblasts (MLFs) reduced YAP1 localization in fibrotic foci. The PF543 inhibition of SPHK1 activity in mice attenuated YAP1 co-localization with FSP1 in lung fibroblasts. In vitro, TGF-β stimulated YAP1 translocation to the nucleus in primary MLFs, and the deletion of Sphk1 or inhibition with PF543 attenuated TGF-β-mediated YAP1 nuclear localization. Moreover, the PF543 inhibition of SPHK1, or the verteporfin inhibition of YAP1, decreased the TGF-β- or BLM-induced mitochondrial reactive oxygen species (mtROS) in human lung fibroblasts (HLFs) and the expression of fibronectin (FN) and alpha-smooth muscle actin (α-SMA). Furthermore, scavenging mtROS with MitoTEMPO attenuated the TGF-β-induced expression of FN and α-SMA. The addition of the S1P antibody to HLFs reduced TGF-β- or S1P-mediated YAP1 activation, mtROS, and the expression of FN and α-SMA. These results suggest a role for SPHK1/S1P signaling in TGF-β-induced YAP1 activation and mtROS generation, resulting in fibroblast activation, a critical driver of pulmonary fibrosis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 21062064 |
| العلاقة: | https://www.mdpi.com/1422-0067/21/6/2064Test; https://doaj.org/toc/1422-0067Test |
| DOI: | 10.3390/ijms21062064 |
| الوصول الحر: | https://doaj.org/article/8ef97aae2dc942b08cd91cea3a3c062aTest |
| رقم الانضمام: | edsdoj.8ef97aae2dc942b08cd91cea3a3c062a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 21062064 |
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| DOI: | 10.3390/ijms21062064 |