Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage
Introduction: Irisin plays an important role in regulating tissue stress, cardiac function, and inflammation. Integrin αvβ5 was recently identified as a receptor for irisin to elicit its physiologic function. It remains unknown whether integrin αvβ5 is required for irisin's function in modulati...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Experimental and Molecular Pathology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0014480023000205 |
| _version_ | 1797390626172436480 |
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| author | Lijiang Wang Supaporn Kulthinee John Slate-Romano Thomas Zhao Hamsa Shanmugam Patrycja M Dubielecka Ling X. Zhang Gangjian Qin Shougang Zhuang Y. Eugene Chin Ting C. Zhao |
| author_facet | Lijiang Wang Supaporn Kulthinee John Slate-Romano Thomas Zhao Hamsa Shanmugam Patrycja M Dubielecka Ling X. Zhang Gangjian Qin Shougang Zhuang Y. Eugene Chin Ting C. Zhao |
| author_sort | Lijiang Wang |
| collection | DOAJ |
| description | Introduction: Irisin plays an important role in regulating tissue stress, cardiac function, and inflammation. Integrin αvβ5 was recently identified as a receptor for irisin to elicit its physiologic function. It remains unknown whether integrin αvβ5 is required for irisin's function in modulating the physiologic response to hemorrhage. The objective of this study is to examine if integrin αvβ5 contributes to the effects of irisin during the hemorrhagic response. Methods: Hemorrhage was induced in mice by achieving a mean arterial blood pressure of 35–45 mmHg for one hour, followed by two hours of resuscitation. Irisin (0.5 μg/kg) was administrated to assess its pharmacologic effects in hemorrhage. Cilengitide, a cyclic Arg-Gly-Asp peptide (cRGDyK) which is an inhibitor of integrin αvβ5, or control RGDS (1 mg/kg) was administered with irisin. In another cohort of mice, the irisin-induced protective effect was examined after knocking down integrin β5 with nanoparticle delivery of integrin β5 sgRNA using CRSIPR/Cas-9 gene editing. Cardiac function and hemodynamics were measured using echocardiography and femoral artery catheterization, respectively. Systemic cytokine releases were measured using Enzyme-linked immunosorbent assay (ELISA). Histological analyses were used to determine tissue damage in myocardium, skeletal muscles, and lung tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was carried out to assess apoptosis in tissues. Results: Hemorrhage induced reduction of integrin αvβ5 in skeletal muscles and repressed recovery of cardiac performance and hemodynamics. Irisin treatment led to significantly improved cardiac function, which was abrogated by treatment with Cilengitide or knockdown of integrin β5. Furthermore, irisin resulted in a marked suppression of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), muscle edema, and inflammatory cells infiltration in myocardium and skeletal muscles, which was attenuated by Cilengitide or knockdown of integrin β5. Irisin-induced reduction of apoptosis in the myocardium, skeletal muscles, and lung, which were attenuated by either the inhibition of integrin αvβ5, or knockdown of integrin β5. Conclusion: Integrin αvβ5 plays an important role for irisin in modulating the protective effect during hemorrhage. |
| first_indexed | 2024-03-08T23:14:35Z |
| format | Article |
| id | doaj.art-9d752d63ef2849ea8271774bf38a64db |
| institution | Directory Open Access Journal |
| issn | 1096-0945 |
| language | English |
| last_indexed | 2024-03-08T23:14:35Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental and Molecular Pathology |
| spelling | doaj.art-9d752d63ef2849ea8271774bf38a64db2023-12-15T07:21:47ZengElsevierExperimental and Molecular Pathology1096-09452023-12-01134104869Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhageLijiang Wang0Supaporn Kulthinee1John Slate-Romano2Thomas Zhao3Hamsa Shanmugam4Patrycja M Dubielecka5Ling X. Zhang6Gangjian Qin7Shougang Zhuang8Y. Eugene Chin9Ting C. Zhao10Department of Plastic Surgery, Rhode Island Hospital, Brown University, USADepartment of Plastic Surgery, Rhode Island Hospital, Brown University, USADepartment of Plastic Surgery, Rhode Island Hospital, Brown University, USABoston University, Boston, MA, USADepartment of Plastic Surgery, Rhode Island Hospital, Brown University, USADepartment of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USADepartment of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USADepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USADepartment of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USASoochow University, Suzhou, ChinaDepartment of Plastic Surgery, Rhode Island Hospital, Brown University, USA; Department of Surgery, Rhode Island Hospital, Brown University, Providence, RI, USA; Corresponding author at: Brown University, Alpert Medical School, Department of Surgery, Department of Plastic and Reconstructive Surgery, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA.Introduction: Irisin plays an important role in regulating tissue stress, cardiac function, and inflammation. Integrin αvβ5 was recently identified as a receptor for irisin to elicit its physiologic function. It remains unknown whether integrin αvβ5 is required for irisin's function in modulating the physiologic response to hemorrhage. The objective of this study is to examine if integrin αvβ5 contributes to the effects of irisin during the hemorrhagic response. Methods: Hemorrhage was induced in mice by achieving a mean arterial blood pressure of 35–45 mmHg for one hour, followed by two hours of resuscitation. Irisin (0.5 μg/kg) was administrated to assess its pharmacologic effects in hemorrhage. Cilengitide, a cyclic Arg-Gly-Asp peptide (cRGDyK) which is an inhibitor of integrin αvβ5, or control RGDS (1 mg/kg) was administered with irisin. In another cohort of mice, the irisin-induced protective effect was examined after knocking down integrin β5 with nanoparticle delivery of integrin β5 sgRNA using CRSIPR/Cas-9 gene editing. Cardiac function and hemodynamics were measured using echocardiography and femoral artery catheterization, respectively. Systemic cytokine releases were measured using Enzyme-linked immunosorbent assay (ELISA). Histological analyses were used to determine tissue damage in myocardium, skeletal muscles, and lung tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was carried out to assess apoptosis in tissues. Results: Hemorrhage induced reduction of integrin αvβ5 in skeletal muscles and repressed recovery of cardiac performance and hemodynamics. Irisin treatment led to significantly improved cardiac function, which was abrogated by treatment with Cilengitide or knockdown of integrin β5. Furthermore, irisin resulted in a marked suppression of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), muscle edema, and inflammatory cells infiltration in myocardium and skeletal muscles, which was attenuated by Cilengitide or knockdown of integrin β5. Irisin-induced reduction of apoptosis in the myocardium, skeletal muscles, and lung, which were attenuated by either the inhibition of integrin αvβ5, or knockdown of integrin β5. Conclusion: Integrin αvβ5 plays an important role for irisin in modulating the protective effect during hemorrhage.http://www.sciencedirect.com/science/article/pii/S0014480023000205HemorrhageIrisin, integrin αvβ5Cardiac functionOrgan failureStresses |
| spellingShingle | Lijiang Wang Supaporn Kulthinee John Slate-Romano Thomas Zhao Hamsa Shanmugam Patrycja M Dubielecka Ling X. Zhang Gangjian Qin Shougang Zhuang Y. Eugene Chin Ting C. Zhao Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage Experimental and Molecular Pathology Hemorrhage Irisin, integrin αvβ5 Cardiac function Organ failure Stresses |
| title | Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage |
| title_full | Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage |
| title_fullStr | Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage |
| title_full_unstemmed | Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage |
| title_short | Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage |
| title_sort | inhibition of integrin alpha v beta 5 mitigates the protective effect induced by irisin in hemorrhage |
| topic | Hemorrhage Irisin, integrin αvβ5 Cardiac function Organ failure Stresses |
| url | http://www.sciencedirect.com/science/article/pii/S0014480023000205 |
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