Endothelial HSPA12B Exerts Protection Against Sepsis-Induced Severe Cardiomyopathy via Suppression of Adhesion Molecule Expression by miR-126
Heat shock protein A12B (HSPA12B) is predominately expressed in endothelial cells (ECs) and has been reported to protect against cardiac dysfunction from endotoxemia or myocardial infarction. This study investigated the mechanisms by which endothelial HSPA12B protects polymicrobial sepsis–induced ca...
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| Format: | Article |
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00566/full |
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| author | Xia Zhang Xiaohui Wang Min Fan Min Fan Fei Tu Fei Tu Kun Yang Kun Yang Tuanzhu Ha Tuanzhu Ha Li Liu John Kalbfleisch John Kalbfleisch David Williams David Williams Chuanfu Li Chuanfu Li |
| author_facet | Xia Zhang Xiaohui Wang Min Fan Min Fan Fei Tu Fei Tu Kun Yang Kun Yang Tuanzhu Ha Tuanzhu Ha Li Liu John Kalbfleisch John Kalbfleisch David Williams David Williams Chuanfu Li Chuanfu Li |
| author_sort | Xia Zhang |
| collection | DOAJ |
| description | Heat shock protein A12B (HSPA12B) is predominately expressed in endothelial cells (ECs) and has been reported to protect against cardiac dysfunction from endotoxemia or myocardial infarction. This study investigated the mechanisms by which endothelial HSPA12B protects polymicrobial sepsis–induced cardiomyopathy. Wild-type (WT) and endothelial HSPA12B knockout (HSPA12B–/–) mice were subjected to polymicrobial sepsis induced by cecal ligation and puncture (CLP). Cecal ligation and puncture sepsis accelerated mortality and caused severe cardiac dysfunction in HSPA12B–/– mice compared with WT septic mice. The levels of adhesion molecules and the infiltrated immune cells in the myocardium of HSPA12B–/– septic mice were markedly greater than in WT septic mice. The levels of microRNA-126 (miR-126), which targets adhesion molecules, in serum exosomes from HSPA12B–/– septic mice were significantly lower than in WT septic mice. Transfection of ECs with adenovirus expressing HSPA12B significantly increased miR-126 levels. Increased miR-126 levels in ECs prevented LPS-stimulated expression of adhesion molecules. In vivo delivery of miR-126 carried by exosomes into the myocardium of HSPA12B–/– mice significantly attenuated CLP sepsis increased levels of adhesion molecules, and improved CLP sepsis–induced cardiac dysfunction. The data suggest that HSPA12B protects against sepsis-induced severe cardiomyopathy via regulating miR-126 expression which targets adhesion molecules, thus decreasing the accumulation of immune cells in the myocardium. |
| first_indexed | 2024-12-11T12:43:00Z |
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| id | doaj.art-e50118cf3bbe4ed1bef2b419bb1232f4 |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T12:43:00Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e50118cf3bbe4ed1bef2b419bb1232f42022-12-22T01:06:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-04-011110.3389/fimmu.2020.00566519735Endothelial HSPA12B Exerts Protection Against Sepsis-Induced Severe Cardiomyopathy via Suppression of Adhesion Molecule Expression by miR-126Xia Zhang0Xiaohui Wang1Min Fan2Min Fan3Fei Tu4Fei Tu5Kun Yang6Kun Yang7Tuanzhu Ha8Tuanzhu Ha9Li Liu10John Kalbfleisch11John Kalbfleisch12David Williams13David Williams14Chuanfu Li15Chuanfu Li16Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesDepartment of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesDepartment of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesThe Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesDepartment of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesThe Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesDepartment of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesThe Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesDepartment of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesThe Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesDepartment of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaThe Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesBiometry and Medical Computing, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesDepartment of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesThe Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesDepartment of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesThe Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United StatesHeat shock protein A12B (HSPA12B) is predominately expressed in endothelial cells (ECs) and has been reported to protect against cardiac dysfunction from endotoxemia or myocardial infarction. This study investigated the mechanisms by which endothelial HSPA12B protects polymicrobial sepsis–induced cardiomyopathy. Wild-type (WT) and endothelial HSPA12B knockout (HSPA12B–/–) mice were subjected to polymicrobial sepsis induced by cecal ligation and puncture (CLP). Cecal ligation and puncture sepsis accelerated mortality and caused severe cardiac dysfunction in HSPA12B–/– mice compared with WT septic mice. The levels of adhesion molecules and the infiltrated immune cells in the myocardium of HSPA12B–/– septic mice were markedly greater than in WT septic mice. The levels of microRNA-126 (miR-126), which targets adhesion molecules, in serum exosomes from HSPA12B–/– septic mice were significantly lower than in WT septic mice. Transfection of ECs with adenovirus expressing HSPA12B significantly increased miR-126 levels. Increased miR-126 levels in ECs prevented LPS-stimulated expression of adhesion molecules. In vivo delivery of miR-126 carried by exosomes into the myocardium of HSPA12B–/– mice significantly attenuated CLP sepsis increased levels of adhesion molecules, and improved CLP sepsis–induced cardiac dysfunction. The data suggest that HSPA12B protects against sepsis-induced severe cardiomyopathy via regulating miR-126 expression which targets adhesion molecules, thus decreasing the accumulation of immune cells in the myocardium.https://www.frontiersin.org/article/10.3389/fimmu.2020.00566/fullendothelial HSPA12Bpolymicrobial sepsiscardiomyopathyexosomesmicroRNAsendothelial adhesion molecules |
| spellingShingle | Xia Zhang Xiaohui Wang Min Fan Min Fan Fei Tu Fei Tu Kun Yang Kun Yang Tuanzhu Ha Tuanzhu Ha Li Liu John Kalbfleisch John Kalbfleisch David Williams David Williams Chuanfu Li Chuanfu Li Endothelial HSPA12B Exerts Protection Against Sepsis-Induced Severe Cardiomyopathy via Suppression of Adhesion Molecule Expression by miR-126 Frontiers in Immunology endothelial HSPA12B polymicrobial sepsis cardiomyopathy exosomes microRNAs endothelial adhesion molecules |
| title | Endothelial HSPA12B Exerts Protection Against Sepsis-Induced Severe Cardiomyopathy via Suppression of Adhesion Molecule Expression by miR-126 |
| title_full | Endothelial HSPA12B Exerts Protection Against Sepsis-Induced Severe Cardiomyopathy via Suppression of Adhesion Molecule Expression by miR-126 |
| title_fullStr | Endothelial HSPA12B Exerts Protection Against Sepsis-Induced Severe Cardiomyopathy via Suppression of Adhesion Molecule Expression by miR-126 |
| title_full_unstemmed | Endothelial HSPA12B Exerts Protection Against Sepsis-Induced Severe Cardiomyopathy via Suppression of Adhesion Molecule Expression by miR-126 |
| title_short | Endothelial HSPA12B Exerts Protection Against Sepsis-Induced Severe Cardiomyopathy via Suppression of Adhesion Molecule Expression by miR-126 |
| title_sort | endothelial hspa12b exerts protection against sepsis induced severe cardiomyopathy via suppression of adhesion molecule expression by mir 126 |
| topic | endothelial HSPA12B polymicrobial sepsis cardiomyopathy exosomes microRNAs endothelial adhesion molecules |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00566/full |
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