Youngheon Park, Jimin Jang, Jooyeon Lee, Hyosin Baek, Jaehyun Park, Sang-Ryul Cha, Se Bi Lee, Sunghun Na, Jae-Woo Kwon, Seok-Ho Hong, Se-Ran Yang
{"title":"环鞘氨醇-1-磷酸引发的间充质干细胞改善lps诱导的小鼠急性肺损伤。","authors":"Youngheon Park, Jimin Jang, Jooyeon Lee, Hyosin Baek, Jaehyun Park, Sang-Ryul Cha, Se Bi Lee, Sunghun Na, Jae-Woo Kwon, Seok-Ho Hong, Se-Ran Yang","doi":"10.15283/ijsc23001","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice.</p><p><strong>Methods and results: </strong>cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC<sup>cP1P</sup>), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC<sup>cP1P</sup> reduce inflammatory response in LPS exposed mice. hdMSC<sup>cP1P</sup> further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC<sup>cP1P</sup> treated mice.</p><p><strong>Conclusions: </strong>Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC<sup>cP1P</sup> provide a therapeutic potential for ALI/ARDS treatment.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"191-201"},"PeriodicalIF":2.5000,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/45/ijsc-16-2-191.PMC10226865.pdf","citationCount":"1","resultStr":"{\"title\":\"Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice.\",\"authors\":\"Youngheon Park, Jimin Jang, Jooyeon Lee, Hyosin Baek, Jaehyun Park, Sang-Ryul Cha, Se Bi Lee, Sunghun Na, Jae-Woo Kwon, Seok-Ho Hong, Se-Ran Yang\",\"doi\":\"10.15283/ijsc23001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice.</p><p><strong>Methods and results: </strong>cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC<sup>cP1P</sup>), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC<sup>cP1P</sup> reduce inflammatory response in LPS exposed mice. hdMSC<sup>cP1P</sup> further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC<sup>cP1P</sup> treated mice.</p><p><strong>Conclusions: </strong>Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC<sup>cP1P</sup> provide a therapeutic potential for ALI/ARDS treatment.</p>\",\"PeriodicalId\":14392,\"journal\":{\"name\":\"International journal of stem cells\",\"volume\":\"16 2\",\"pages\":\"191-201\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2023-05-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/45/ijsc-16-2-191.PMC10226865.pdf\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International journal of stem cells\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.15283/ijsc23001\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of stem cells","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.15283/ijsc23001","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
Background and objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice.
Methods and results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSCcP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSCcP1P reduce inflammatory response in LPS exposed mice. hdMSCcP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSCcP1P treated mice.
Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSCcP1P provide a therapeutic potential for ALI/ARDS treatment.
期刊介绍:
International Journal of Stem Cells (Int J Stem Cells), a peer-reviewed open access journal, principally aims to provide a forum for investigators in the field of stem cell biology to present their research findings and share their visions and opinions. Int J Stem Cells covers all aspects of stem cell biology including basic, clinical and translational research on genetics, biochemistry, and physiology of various types of stem cells including embryonic, adult and induced stem cells. Reports on epigenetics, genomics, proteomics, metabolomics of stem cells are welcome as well. Int J Stem Cells also publishes review articles, technical reports and treatise on ethical issues.