Involvement of Lysophospholipids in Pulmonary Vascular Functions and Diseases
Extracellular lysophospholipids (lysophosphatidic acid, lysophosphatidylcholine, sphingosine 1-phosphate, etc.), which are synthesized from phospholipids in the cell membrane, act as lipid mediators, and mediate various cellular responses in constituent cells in the respiratory system, such as contr...
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MDPI AG
2024-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/1/124 |
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| author | Hiroaki Kume Rina Harigane Mami Rikimaru |
| author_facet | Hiroaki Kume Rina Harigane Mami Rikimaru |
| author_sort | Hiroaki Kume |
| collection | DOAJ |
| description | Extracellular lysophospholipids (lysophosphatidic acid, lysophosphatidylcholine, sphingosine 1-phosphate, etc.), which are synthesized from phospholipids in the cell membrane, act as lipid mediators, and mediate various cellular responses in constituent cells in the respiratory system, such as contraction, proliferation, migration, and cytoskeletal organization. In addition to these effects, the expression of the adhesion molecules is enhanced by these extracellular lysophospholipids in pulmonary endothelial cells. These effects are exerted via specific G protein-coupled receptors. Rho, Ras, and phospholipase C (PLC) have been proven to be their signaling pathways, related to Ca<sup>2+</sup> signaling due to Ca<sup>2+</sup> dynamics and Ca<sup>2+</sup> sensitization. Therefore, lysophospholipids probably induce pulmonary vascular remodeling through phenotype changes in smooth muscle cells, endothelial cells, and fibroblasts, likely resulting in acute respiratory distress syndrome due to vascular leak, pulmonary hypertension, and pulmonary fibrosis. Moreover, lysophospholipids induce the recruitment of inflammatory cells to the lungs via the enhancement of adhesion molecules in endothelial cells, potentially leading to the development of asthma. These results demonstrate that lysophospholipids may be novel therapeutic targets not only for injury, fibrosis, and hypertension in the lung, but also for asthma. In this review, we discuss the mechanisms of the effects of lysophospholipids on the respiratory system, and the possibility of precision medicine targeting lysophospholipids as treatable traits of these diseases. |
| first_indexed | 2024-03-08T09:57:39Z |
| format | Article |
| id | doaj.art-3f58643cad8847b9a7acf1e7c592789e |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-08T09:57:39Z |
| publishDate | 2024-01-01 |
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| spelling | doaj.art-3f58643cad8847b9a7acf1e7c592789e2024-01-29T13:47:20ZengMDPI AGBiomedicines2227-90592024-01-0112112410.3390/biomedicines12010124Involvement of Lysophospholipids in Pulmonary Vascular Functions and DiseasesHiroaki Kume0Rina Harigane1Mami Rikimaru2Department of Infectious Diseases and Respiratory Medicine, Fukushima Medical University Aizu Medical Center, 21-2 Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu City 969-3492, Fukushima, JapanDepartment of Infectious Diseases and Respiratory Medicine, Fukushima Medical University Aizu Medical Center, 21-2 Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu City 969-3492, Fukushima, JapanDepartment of Infectious Diseases and Respiratory Medicine, Fukushima Medical University Aizu Medical Center, 21-2 Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu City 969-3492, Fukushima, JapanExtracellular lysophospholipids (lysophosphatidic acid, lysophosphatidylcholine, sphingosine 1-phosphate, etc.), which are synthesized from phospholipids in the cell membrane, act as lipid mediators, and mediate various cellular responses in constituent cells in the respiratory system, such as contraction, proliferation, migration, and cytoskeletal organization. In addition to these effects, the expression of the adhesion molecules is enhanced by these extracellular lysophospholipids in pulmonary endothelial cells. These effects are exerted via specific G protein-coupled receptors. Rho, Ras, and phospholipase C (PLC) have been proven to be their signaling pathways, related to Ca<sup>2+</sup> signaling due to Ca<sup>2+</sup> dynamics and Ca<sup>2+</sup> sensitization. Therefore, lysophospholipids probably induce pulmonary vascular remodeling through phenotype changes in smooth muscle cells, endothelial cells, and fibroblasts, likely resulting in acute respiratory distress syndrome due to vascular leak, pulmonary hypertension, and pulmonary fibrosis. Moreover, lysophospholipids induce the recruitment of inflammatory cells to the lungs via the enhancement of adhesion molecules in endothelial cells, potentially leading to the development of asthma. These results demonstrate that lysophospholipids may be novel therapeutic targets not only for injury, fibrosis, and hypertension in the lung, but also for asthma. In this review, we discuss the mechanisms of the effects of lysophospholipids on the respiratory system, and the possibility of precision medicine targeting lysophospholipids as treatable traits of these diseases.https://www.mdpi.com/2227-9059/12/1/124lysophosphatidic acidlysophosphadidylcholinesphingosine 1-phosphatepulmonary vascular smooth musclepulmonary endothelial cellspulmonary fibroblasts |
| spellingShingle | Hiroaki Kume Rina Harigane Mami Rikimaru Involvement of Lysophospholipids in Pulmonary Vascular Functions and Diseases Biomedicines lysophosphatidic acid lysophosphadidylcholine sphingosine 1-phosphate pulmonary vascular smooth muscle pulmonary endothelial cells pulmonary fibroblasts |
| title | Involvement of Lysophospholipids in Pulmonary Vascular Functions and Diseases |
| title_full | Involvement of Lysophospholipids in Pulmonary Vascular Functions and Diseases |
| title_fullStr | Involvement of Lysophospholipids in Pulmonary Vascular Functions and Diseases |
| title_full_unstemmed | Involvement of Lysophospholipids in Pulmonary Vascular Functions and Diseases |
| title_short | Involvement of Lysophospholipids in Pulmonary Vascular Functions and Diseases |
| title_sort | involvement of lysophospholipids in pulmonary vascular functions and diseases |
| topic | lysophosphatidic acid lysophosphadidylcholine sphingosine 1-phosphate pulmonary vascular smooth muscle pulmonary endothelial cells pulmonary fibroblasts |
| url | https://www.mdpi.com/2227-9059/12/1/124 |
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