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CD47 antibody suppresses isoproterenol-induced cardiac hypertrophy through activation of autophagy.

ABSTRACT: In this study, we investigated whether CD47 antibody could attenuate isoproterenol (ISO)-induced cardiac hypertrophy in mice and H9C2 cells. Cardiac hypertrophy was induced by intraperitoneal (i.p.) injection of ISO (60 mg.kg-1.d-1 in 100 µl of sterile normal saline) daily for 14 days, and cell hypertrophy was induced by ISO (10-5 mol/l) for 48 h. The injury was confirmed by increased levels of lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB), increased heart-to-body weight (HW/BW) ratio and visible cardiac fibrosis. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Autophagic flux in H9c2 cells was monitored by TEM and mRFP-GFP-LC3 virus transfection. The expression levels of Cleaved caspase-3, Cleaved caspase-9 and autophagy-related proteins were detected by Western blotting. CD47 antibody significantly limited ISO-induced increases in LDH, CK-MB, HW/BW ratio and attenuated cardiac fibrosis, oxidative stress, and apoptosis in the heart; CD47 antibody promoted autophagy flow and decreased cell apoptosis in cardiac tissues. Moreover, autophagy inhibitor chloroquine (CQ) reversed the effect of CD47 antibody treatment. In conclusion, CD47 antibody reduced ISO-induced cardiac hypertrophy by improving autophagy flux and rescuing autophagic clearance.

SUBMITTER: Li Y

PROVIDER: S-EPMC7540123 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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CD47 antibody suppresses isoproterenol-induced cardiac hypertrophy through activation of autophagy.

Li Yong Y Chen Xuguan X Li Peng P Xiao Qianxuan Q Hou Daorong D Kong Xiangqing X

American journal of translational research 20200915 9

In this study, we investigated whether CD47 antibody could attenuate isoproterenol (ISO)-induced cardiac hypertrophy in mice and H9C2 cells. Cardiac hypertrophy was induced by intraperitoneal (i.p.) injection of ISO (60 mg.kg-1.d-1 in 100 µl of sterile normal saline) daily for 14 days, and cell hypertrophy was induced by ISO (10-5 mol/l) for 48 h. The injury was confirmed by increased levels of lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB), increased ...[more]

PMID: 33042468

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Project description:Intercellular communication is critical for integrating complex signals in multicellular eukaryotes. Vascular endothelial cells and T lymphocytes closely interact during the recirculation and trans-endothelial migration of T cells. In addition to direct cell-cell contact, we show that T cell derived extracellular vesicles can interact with endothelial cells and modulate their cellular functions. Thrombospondin-1 and its receptor CD47 are expressed on exosomes/ectosomes derived from T cells, and these extracellular vesicles are internalized and modulate signaling in both T cells and endothelial cells. Extracellular vesicles released from cells expressing or lacking CD47 differentially regulate activation of T cells induced by engaging the T cell receptor. Similarly, T cell-derived extracellular vesicles modulate endothelial cell responses to vascular endothelial growth factor and tube formation in a CD47-dependent manner. Uptake of T cell derived extracellular vesicles by recipient endothelial cells globally alters gene expression in a CD47-dependent manner. CD47 also regulates the mRNA content of extracellular vesicles in a manner consistent with some of the resulting alterations in target endothelial cell gene expression. Therefore, the thrombospondin-1 receptor CD47 directly or indirectly regulates intercellular communication mediated by the transfer of extracellular vesicles between vascular cells. Treatment with B6H12 antibody inhibited co-immunoprecipitation of EGFR with CD47 and inhibited EGF-induced EGFR tyrosine phosphorylation. B6H12 treatment of bCSC also suppressed asymmetric cell division and cell proliferation and up-regulated caspase 3/7 activity. Correspondingly, caspase-7 cleavage in human breast cancers correlated with CD47 expression. Our data shows that B6H12 specifically targets bCSCs but not differentiated cancer cells, and this CD47 signaling is independent of SIRPÎ±. Three replicates of each condition were generated. Three replicates of each MDA-231 attached cells (differentiated), MDA-231 in suspension cells (bCSC), MDA-231 in suspension cells (bCSC) treated with Control Antibody and MDA-231 in suspension cells (bCSC) treated with B6H12 Antibody.

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CD47 antibody suppresses isoproterenol-induced cardiac hypertrophy through activation of autophagy.

Publications

CD47 antibody suppresses isoproterenol-induced cardiac hypertrophy through activation of autophagy.

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