دورية أكاديمية
أعرض في EDS

Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage.

التفاصيل البيبلوغرافية
العنوان: Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage.
المؤلفون: Wang L; Department of Plastic Surgery, Rhode Island Hospital, Brown University, USA., Kulthinee S; Department of Plastic Surgery, Rhode Island Hospital, Brown University, USA., Slate-Romano J; Department of Plastic Surgery, Rhode Island Hospital, Brown University, USA., Zhao T; Boston University, Boston, MA, USA., Shanmugam H; Department of Plastic Surgery, Rhode Island Hospital, Brown University, USA., Dubielecka PM; Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA., Zhang LX; Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA., Qin G; Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA., Zhuang S; Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA., Chin YE; Soochow University, Suzhou, China., Zhao TC; Department of Plastic Surgery, Rhode Island Hospital, Brown University, USA; Department of Surgery, Rhode Island Hospital, Brown University, Providence, RI, USA. Electronic address: Ting_Zhao@Brown.Edu.
المصدر: Experimental and molecular pathology [Exp Mol Pathol] 2023 Dec; Vol. 134, pp. 104869. Date of Electronic Publication: 2023 Sep 27.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0370711 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0945 (Electronic) Linking ISSN: 00144800 NLM ISO Abbreviation: Exp Mol Pathol Subsets: MEDLINE
أسماء مطبوعة: Publication: <2000- > : Amsteram : Elsevier
Original Publication: New York : Academic Press
مواضيع طبية MeSH: Fibronectins*/genetics , Fibronectins*/pharmacology , Integrin alphaV*, Animals ; Humans ; Mice ; Hemorrhage ; RNA, Guide, CRISPR-Cas Systems
مستخلص: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01 GM141339 United States GM NIGMS NIH HHS; R01 HL089405 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: Cardiac function; Hemorrhage; Irisin, integrin αvβ5; Organ failure; Stresses
المشرفين على المادة: 0 (Fibronectins)
0 (Integrin alphaV)
0 (integrin alphaVbeta5)
0 (RNA, Guide, CRISPR-Cas Systems)
0 (FNDC5 protein, mouse)
تواريخ الأحداث: Date Created: 20230910 Date Completed: 20231218 Latest Revision: 20240415
رمز التحديث: 20240415
مُعرف محوري في PubMed: PMC10939993
DOI: 10.1016/j.yexmp.2023.104869
PMID: 37690529
قاعدة البيانات: MEDLINE
الوصف
تدمد:1096-0945
DOI:10.1016/j.yexmp.2023.104869