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Sphingosine Kinase 1 Regulates the Pulmonary Vascular Immune Response.
- Source :
-
Cell biochemistry and biophysics [Cell Biochem Biophys] 2021 Sep; Vol. 79 (3), pp. 517-529. Date of Electronic Publication: 2021 Jun 16. - Publication Year :
- 2021
-
Abstract
- The aberrant proliferation of pulmonary artery smooth muscle (PASMCs) cells is a defining characteristic of pulmonary arterial hypertension (PAH) and leads to increased vascular resistance, elevated pulmonary pressure, and right heart failure. The sphingosine kinase 1 (SPHK1)/sphingosine-1 phosphate/sphingosine-1 phosphate receptor 2 pathway promotes vascular remodeling and induces PAH. The aim of this study was to identify genes and cellular processes that are modulated by over-expression of SPHK1 in human PASMCs (hPASMCs). RNA was purified and submitted for RNA sequencing to identify differentially expressed genes. Using a corrected p-value threshold of <0.05, there were 294 genes significantly up-regulated while 179 were significantly down-regulated. Predicted effects of these differentially expressed genes were evaluated using the freeware tool Enrichr to assess general gene set over-representation (enrichment) and ingenuity pathway analysis (IPA™) for upstream regulator predictions. We found a strong change in genes that regulated the cellular immune response. IL6, STAT1, and PARP9 were elevated in response to SPHK1 over-expression in hPASMCs. The gene set enrichment mapped to a few immune-modulatory signaling networks, including IFNG. Furthermore, PARP9 and STAT1 protein were elevated in primary hPASMCs isolated from PAH patients. In conclusion, these data suggest a role of Sphk1 regulates pulmonary vascular immune response in PAH.<br /> (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Humans
Interferon-gamma metabolism
Interleukin-6 metabolism
Interleukin-6 genetics
Myocytes, Smooth Muscle metabolism
Signal Transduction
Cells, Cultured
Sphingosine-1-Phosphate Receptors metabolism
Sphingosine-1-Phosphate Receptors genetics
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular cytology
Sphingosine analogs & derivatives
Sphingosine metabolism
Phosphotransferases (Alcohol Group Acceptor) metabolism
Phosphotransferases (Alcohol Group Acceptor) genetics
Pulmonary Artery metabolism
Pulmonary Artery cytology
STAT1 Transcription Factor metabolism
STAT1 Transcription Factor genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1559-0283
- Volume :
- 79
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cell biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 34133010
- Full Text :
- https://doi.org/10.1007/s12013-021-01006-8