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Adropin inhibits the progression of atherosclerosis in ApoE(-/-)/Enho(-/-) mice by regulating endothelial-to-mesenchymal transition
Adropin, a secreted protein, coded by energy homeostasis-associated gene (Enho), is recently reported to modulate atherogenesis, with endothelial-to-mesenchymal transition (EndMT) involved in the early process. We explored whether adropin may alleviate atherosclerosis by regulating EndMT. We found t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616072/ https://www.ncbi.nlm.nih.gov/pubmed/37903785 http://dx.doi.org/10.1038/s41420-023-01697-3 |
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author | Ying, Teng Wu, LingZhen Lan, TingXiang Wei, ZhiXiong Hu, DanQing Ke, YiLang Jiang, Qiong Fang, Jun |
author_facet | Ying, Teng Wu, LingZhen Lan, TingXiang Wei, ZhiXiong Hu, DanQing Ke, YiLang Jiang, Qiong Fang, Jun |
author_sort | Ying, Teng |
collection | PubMed |
description | Adropin, a secreted protein, coded by energy homeostasis-associated gene (Enho), is recently reported to modulate atherogenesis, with endothelial-to-mesenchymal transition (EndMT) involved in the early process. We explored whether adropin may alleviate atherosclerosis by regulating EndMT. We found that an intraperitoneal injection of adropin [105 μg/(kg·d) for 13 weeks] inhibited the progression of high-fat diet (HFD)-induced aortic atherosclerosis in apolipoprotein E-deficient mice (ApoE(–/–)) and those with double gene deletion (ApoE(–/–)/Enho(–/–)), as detected by Oil Red O and haematoxylin-eosin staining. In the aortas of ApoE(–/–) mouse, adropin treatment ameliorated the decrease in the mRNA expression of endothelial cell markers (leukocyte differentiation antigen 31, CD31, and vascular endothelial cadherin, VE-cadherin), but increased that of EndMT markers (alpha smooth muscle actin, α-SMA, and fibroblasts specific protein-1). In vitro, an adropin treatment (30 ng/ml) arrested the hydrogen peroxide (H(2)O(2))-induced EndMT in human umbilical vein endothelial cells (HUVECs), attenuated the morphological changes of HUVECs, reduced the number of immunofluorescence-positive α-SMA, increased the mRNA and protein expressions of CD31 and VE-cadherin, and decreased those of α-SMA. Furthermore, the adropin treatment decreased the mRNA and protein expressions of transforming growth factor (TGF)-β1 and TGF-β2, and suppressed the phosphorylation of downstream signal protein Smad2/3 in HUVECs. These mitigative effects of adropin on H(2)O(2)-induced EndMT were reversed by the transfection of TGF-β plasmid. The findings signify that adropin treatment may alleviate the atherosclerosis in ApoE(–/–)/Enho(–/–) mice by inhibiting EndMT via the TGF-β/Smad2/3 signaling pathway. |
format | Online Article Text |
id | pubmed-10616072 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106160722023-11-01 Adropin inhibits the progression of atherosclerosis in ApoE(-/-)/Enho(-/-) mice by regulating endothelial-to-mesenchymal transition Ying, Teng Wu, LingZhen Lan, TingXiang Wei, ZhiXiong Hu, DanQing Ke, YiLang Jiang, Qiong Fang, Jun Cell Death Discov Article Adropin, a secreted protein, coded by energy homeostasis-associated gene (Enho), is recently reported to modulate atherogenesis, with endothelial-to-mesenchymal transition (EndMT) involved in the early process. We explored whether adropin may alleviate atherosclerosis by regulating EndMT. We found that an intraperitoneal injection of adropin [105 μg/(kg·d) for 13 weeks] inhibited the progression of high-fat diet (HFD)-induced aortic atherosclerosis in apolipoprotein E-deficient mice (ApoE(–/–)) and those with double gene deletion (ApoE(–/–)/Enho(–/–)), as detected by Oil Red O and haematoxylin-eosin staining. In the aortas of ApoE(–/–) mouse, adropin treatment ameliorated the decrease in the mRNA expression of endothelial cell markers (leukocyte differentiation antigen 31, CD31, and vascular endothelial cadherin, VE-cadherin), but increased that of EndMT markers (alpha smooth muscle actin, α-SMA, and fibroblasts specific protein-1). In vitro, an adropin treatment (30 ng/ml) arrested the hydrogen peroxide (H(2)O(2))-induced EndMT in human umbilical vein endothelial cells (HUVECs), attenuated the morphological changes of HUVECs, reduced the number of immunofluorescence-positive α-SMA, increased the mRNA and protein expressions of CD31 and VE-cadherin, and decreased those of α-SMA. Furthermore, the adropin treatment decreased the mRNA and protein expressions of transforming growth factor (TGF)-β1 and TGF-β2, and suppressed the phosphorylation of downstream signal protein Smad2/3 in HUVECs. These mitigative effects of adropin on H(2)O(2)-induced EndMT were reversed by the transfection of TGF-β plasmid. The findings signify that adropin treatment may alleviate the atherosclerosis in ApoE(–/–)/Enho(–/–) mice by inhibiting EndMT via the TGF-β/Smad2/3 signaling pathway. Nature Publishing Group UK 2023-10-31 /pmc/articles/PMC10616072/ /pubmed/37903785 http://dx.doi.org/10.1038/s41420-023-01697-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ying, Teng Wu, LingZhen Lan, TingXiang Wei, ZhiXiong Hu, DanQing Ke, YiLang Jiang, Qiong Fang, Jun Adropin inhibits the progression of atherosclerosis in ApoE(-/-)/Enho(-/-) mice by regulating endothelial-to-mesenchymal transition |
title | Adropin inhibits the progression of atherosclerosis in ApoE(-/-)/Enho(-/-) mice by regulating endothelial-to-mesenchymal transition |
title_full | Adropin inhibits the progression of atherosclerosis in ApoE(-/-)/Enho(-/-) mice by regulating endothelial-to-mesenchymal transition |
title_fullStr | Adropin inhibits the progression of atherosclerosis in ApoE(-/-)/Enho(-/-) mice by regulating endothelial-to-mesenchymal transition |
title_full_unstemmed | Adropin inhibits the progression of atherosclerosis in ApoE(-/-)/Enho(-/-) mice by regulating endothelial-to-mesenchymal transition |
title_short | Adropin inhibits the progression of atherosclerosis in ApoE(-/-)/Enho(-/-) mice by regulating endothelial-to-mesenchymal transition |
title_sort | adropin inhibits the progression of atherosclerosis in apoe(-/-)/enho(-/-) mice by regulating endothelial-to-mesenchymal transition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616072/ https://www.ncbi.nlm.nih.gov/pubmed/37903785 http://dx.doi.org/10.1038/s41420-023-01697-3 |
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