The Lung Alveolar Cell (LAC) miRNome and Gene Expression Profile of the SP-A-KO Mice After Infection With and Without Rescue With Human Surfactant Protein-A2 (1A0)
Human surfactant protein (SP)-A1 and SP-A2 exhibit differential qualitative and quantitative effects on the alveolar macrophage (AM), including a differential impact on the AM miRNome. Moreover, SP-A rescue (treatment) of SP-A-knockout (KO) infected mice impoves survival. Here, we studied for the fi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.854434/full |
| _version_ | 1811327434762485760 |
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| author | Nithyananda Thorenoor Nithyananda Thorenoor Joanna Floros Joanna Floros |
| author_facet | Nithyananda Thorenoor Nithyananda Thorenoor Joanna Floros Joanna Floros |
| author_sort | Nithyananda Thorenoor |
| collection | DOAJ |
| description | Human surfactant protein (SP)-A1 and SP-A2 exhibit differential qualitative and quantitative effects on the alveolar macrophage (AM), including a differential impact on the AM miRNome. Moreover, SP-A rescue (treatment) of SP-A-knockout (KO) infected mice impoves survival. Here, we studied for the first time the role of exogenous SP-A protein treatment on the regulation of lung alveolar cell (LAC) miRNome, the miRNA-RNA targets, and gene expression of SP-A-KO infected mice of both sexes. Toward this, SP-A-KO mice of both sexes were infected with Klebsiella pneumoniae, and half of them were also treated with SP-A2 (1A0). After 6 h of infection/SP-A treatment, the expression levels and pathways of LAC miRNAs, genes, and target miRNA-mRNAs were studied in both groups. We found 1) significant differences in the LAC miRNome, genes, and miRNA-mRNA targets in terms of sex, infection, and infection plus SP-A2 (1A0) protein rescue; 2) an increase in the majority of miRNA-mRNA targets in both study groups in KO male vs. female mice and involvement of the miRNA-mRNA targets in pathways of inflammation, antiapoptosis, and cell cycle; 3) genes with significant changes to be involved in TP-53, tumor necrosis factor (TNF), and cell cycle signaling nodes; 4) when significant changes in the expression of molecules from all analyses (miRNAs, miRNA-mRNA targets, and genes) were considered, two signaling pathways, the TNF and cell cycle, referred to as “integrated pathways” were shown to be significant; 5) the cell cycle pathway to be present in all comparisons made. Because SP-A could be used therapeutically in pulmonary diseases, it is important to understand the molecules and pathways involved in response to an SP-A acute treatment. The information obtained contributes to this end and may help to gain insight especially in the case of infection. |
| first_indexed | 2024-04-13T15:07:53Z |
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| id | doaj.art-766e94688a7b46babdfdc6805519e2c0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T15:07:53Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-766e94688a7b46babdfdc6805519e2c02022-12-22T02:42:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.854434854434The Lung Alveolar Cell (LAC) miRNome and Gene Expression Profile of the SP-A-KO Mice After Infection With and Without Rescue With Human Surfactant Protein-A2 (1A0)Nithyananda Thorenoor0Nithyananda Thorenoor1Joanna Floros2Joanna Floros3Department of Pediatrics, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesDepartment of Biochemistry and Molecular Biology, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesDepartment of Pediatrics, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesDepartment of Obstetrics and Gynecology, College of Medicine, The Pennsylvania State University, Hershey, PA, United StatesHuman surfactant protein (SP)-A1 and SP-A2 exhibit differential qualitative and quantitative effects on the alveolar macrophage (AM), including a differential impact on the AM miRNome. Moreover, SP-A rescue (treatment) of SP-A-knockout (KO) infected mice impoves survival. Here, we studied for the first time the role of exogenous SP-A protein treatment on the regulation of lung alveolar cell (LAC) miRNome, the miRNA-RNA targets, and gene expression of SP-A-KO infected mice of both sexes. Toward this, SP-A-KO mice of both sexes were infected with Klebsiella pneumoniae, and half of them were also treated with SP-A2 (1A0). After 6 h of infection/SP-A treatment, the expression levels and pathways of LAC miRNAs, genes, and target miRNA-mRNAs were studied in both groups. We found 1) significant differences in the LAC miRNome, genes, and miRNA-mRNA targets in terms of sex, infection, and infection plus SP-A2 (1A0) protein rescue; 2) an increase in the majority of miRNA-mRNA targets in both study groups in KO male vs. female mice and involvement of the miRNA-mRNA targets in pathways of inflammation, antiapoptosis, and cell cycle; 3) genes with significant changes to be involved in TP-53, tumor necrosis factor (TNF), and cell cycle signaling nodes; 4) when significant changes in the expression of molecules from all analyses (miRNAs, miRNA-mRNA targets, and genes) were considered, two signaling pathways, the TNF and cell cycle, referred to as “integrated pathways” were shown to be significant; 5) the cell cycle pathway to be present in all comparisons made. Because SP-A could be used therapeutically in pulmonary diseases, it is important to understand the molecules and pathways involved in response to an SP-A acute treatment. The information obtained contributes to this end and may help to gain insight especially in the case of infection.https://www.frontiersin.org/articles/10.3389/fimmu.2022.854434/fullsurfactant protein A2lung alveolar cellsalveolar macrophagesKlebsiella pneumoniaemiRNomegene expression |
| spellingShingle | Nithyananda Thorenoor Nithyananda Thorenoor Joanna Floros Joanna Floros The Lung Alveolar Cell (LAC) miRNome and Gene Expression Profile of the SP-A-KO Mice After Infection With and Without Rescue With Human Surfactant Protein-A2 (1A0) Frontiers in Immunology surfactant protein A2 lung alveolar cells alveolar macrophages Klebsiella pneumoniae miRNome gene expression |
| title | The Lung Alveolar Cell (LAC) miRNome and Gene Expression Profile of the SP-A-KO Mice After Infection With and Without Rescue With Human Surfactant Protein-A2 (1A0) |
| title_full | The Lung Alveolar Cell (LAC) miRNome and Gene Expression Profile of the SP-A-KO Mice After Infection With and Without Rescue With Human Surfactant Protein-A2 (1A0) |
| title_fullStr | The Lung Alveolar Cell (LAC) miRNome and Gene Expression Profile of the SP-A-KO Mice After Infection With and Without Rescue With Human Surfactant Protein-A2 (1A0) |
| title_full_unstemmed | The Lung Alveolar Cell (LAC) miRNome and Gene Expression Profile of the SP-A-KO Mice After Infection With and Without Rescue With Human Surfactant Protein-A2 (1A0) |
| title_short | The Lung Alveolar Cell (LAC) miRNome and Gene Expression Profile of the SP-A-KO Mice After Infection With and Without Rescue With Human Surfactant Protein-A2 (1A0) |
| title_sort | lung alveolar cell lac mirnome and gene expression profile of the sp a ko mice after infection with and without rescue with human surfactant protein a2 1a0 |
| topic | surfactant protein A2 lung alveolar cells alveolar macrophages Klebsiella pneumoniae miRNome gene expression |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.854434/full |
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