Clusterin ameliorates diabetic atherosclerosis by suppressing macrophage pyroptosis and activation
BackgroundIt has been demonstrated that clusterin (CLU) is a protective protein involved in a variety of diseases and disorders. However, the role of CLU in diabetic atherosclerosis is not elucidative. The objective of this study is to investigate the role of CLU in diabetic atherosclerosis and the...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1536132/full |
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| author | Lingling Xuan Lulu Ren Xiaoxu Kang Rui Chang Wen Zhang Lili Gong Lihong Liu Lihong Liu |
| author_facet | Lingling Xuan Lulu Ren Xiaoxu Kang Rui Chang Wen Zhang Lili Gong Lihong Liu Lihong Liu |
| author_sort | Lingling Xuan |
| collection | DOAJ |
| description | BackgroundIt has been demonstrated that clusterin (CLU) is a protective protein involved in a variety of diseases and disorders. However, the role of CLU in diabetic atherosclerosis is not elucidative. The objective of this study is to investigate the role of CLU in diabetic atherosclerosis and the molecular mechanisms.MethodIn in vivo experiments, Clu knockout and overexpressed murine models were used to investigate the role of Clu in diabetic atherosclerosis. Atherosclerotic plaque formation was determined by hematoxylin-eosin (H&E) staining and Oil Red O staining. F4/80 and CD68 levels were determined by immunohistochemical staining. Transmission electron microscopy was used to observe changes in cell pyroptosis morphology. NLRP3 and IL-1β levels were determined by Western blot and immunofluorescence staining. In in vitro experiments, TNF-α, IL-6, and IL-1β levels in THP-1 derived macrophages were determined by real-time qPCR and ELISA.ResultsWe found that Clu-overexpression reduced while Clu knockout promoted atherosclerotic plaque formation, macrophage infiltration and inflammatory factor expression in mouse aortic plaques. Consistently, CLU overexpression inhibits the production of TNF-α, IL-6, and IL-1β in THP-1 derived macrophages. Moreover, Clu inhibited the release of inflammatory factors and macrophage pyroptosis in diabetic atherosclerosis murine models.ConclusionOur study revealed that CLU could ameliorate diabetic atherosclerosis via suppressing inflammatory factors release and pyroptosis of macrophage. CLU may be a promising therapeutic target for diabetic atherosclerosis. |
| format | Article |
| id | doaj-art-d934a75c177e4b77aac5878444c4fe3f |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-d934a75c177e4b77aac5878444c4fe3f2025-08-20T03:13:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15361321536132Clusterin ameliorates diabetic atherosclerosis by suppressing macrophage pyroptosis and activationLingling Xuan0Lulu Ren1Xiaoxu Kang2Rui Chang3Wen Zhang4Lili Gong5Lihong Liu6Lihong Liu7Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaDepartment of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Capital Medical University, Beijing, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Capital Medical University, Beijing, ChinaDepartment of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Capital Medical University, Beijing, ChinaInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, Capital Medical University, Beijing, ChinaDepartment of Pharmacy, China-Japan Friendship Hospital, Beijing, ChinaBackgroundIt has been demonstrated that clusterin (CLU) is a protective protein involved in a variety of diseases and disorders. However, the role of CLU in diabetic atherosclerosis is not elucidative. The objective of this study is to investigate the role of CLU in diabetic atherosclerosis and the molecular mechanisms.MethodIn in vivo experiments, Clu knockout and overexpressed murine models were used to investigate the role of Clu in diabetic atherosclerosis. Atherosclerotic plaque formation was determined by hematoxylin-eosin (H&E) staining and Oil Red O staining. F4/80 and CD68 levels were determined by immunohistochemical staining. Transmission electron microscopy was used to observe changes in cell pyroptosis morphology. NLRP3 and IL-1β levels were determined by Western blot and immunofluorescence staining. In in vitro experiments, TNF-α, IL-6, and IL-1β levels in THP-1 derived macrophages were determined by real-time qPCR and ELISA.ResultsWe found that Clu-overexpression reduced while Clu knockout promoted atherosclerotic plaque formation, macrophage infiltration and inflammatory factor expression in mouse aortic plaques. Consistently, CLU overexpression inhibits the production of TNF-α, IL-6, and IL-1β in THP-1 derived macrophages. Moreover, Clu inhibited the release of inflammatory factors and macrophage pyroptosis in diabetic atherosclerosis murine models.ConclusionOur study revealed that CLU could ameliorate diabetic atherosclerosis via suppressing inflammatory factors release and pyroptosis of macrophage. CLU may be a promising therapeutic target for diabetic atherosclerosis.https://www.frontiersin.org/articles/10.3389/fphar.2025.1536132/fullclusterinatherosclerosisdiabetesmacrophage pyroptosisinflammation |
| spellingShingle | Lingling Xuan Lulu Ren Xiaoxu Kang Rui Chang Wen Zhang Lili Gong Lihong Liu Lihong Liu Clusterin ameliorates diabetic atherosclerosis by suppressing macrophage pyroptosis and activation Frontiers in Pharmacology clusterin atherosclerosis diabetes macrophage pyroptosis inflammation |
| title | Clusterin ameliorates diabetic atherosclerosis by suppressing macrophage pyroptosis and activation |
| title_full | Clusterin ameliorates diabetic atherosclerosis by suppressing macrophage pyroptosis and activation |
| title_fullStr | Clusterin ameliorates diabetic atherosclerosis by suppressing macrophage pyroptosis and activation |
| title_full_unstemmed | Clusterin ameliorates diabetic atherosclerosis by suppressing macrophage pyroptosis and activation |
| title_short | Clusterin ameliorates diabetic atherosclerosis by suppressing macrophage pyroptosis and activation |
| title_sort | clusterin ameliorates diabetic atherosclerosis by suppressing macrophage pyroptosis and activation |
| topic | clusterin atherosclerosis diabetes macrophage pyroptosis inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1536132/full |
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