Wei Sheng Siew, Yin Quan Tang, Bey Hing Goh, Wei Hsum Yap
{"title":"衰老标记 p16INK4a 可促进巨噬细胞泡沫细胞的形成。","authors":"Wei Sheng Siew, Yin Quan Tang, Bey Hing Goh, Wei Hsum Yap","doi":"10.1007/s11033-024-09946-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The senescence marker p16INK4a, which constitutes part of the genome 9p21.3 cardiovascular disease (CVD) risk allele, is believed to play a role in foam cells formation. This study aims to unravel the role of p16INK4a in mediating macrophage foam cells formation, cellular senescence, and autophagy lysosomal functions.</p><p><strong>Methods: </strong>The mammalian expression plasmid pCMV-p16INK4a was used to induce p16INK4a overexpression in THP-1 macrophages. Next, wild-type and p16INK4a-overexpressed macrophages were incubated with oxidized LDL to induce foam cells formation. Lipids accumulation was evaluated using Oil-red-O staining and cholesterol efflux assay, as well as expression of scavenger receptors CD36 and LOX-1. Cellular senescence in macrophage foam cells were determined through analysis of senescence-associated β-galactosidase activity and other SASP factors expression. Meanwhile, autophagy induction was assessed through detection of autophagosome formation and LC3B/p62 markers expression.</p><p><strong>Results: </strong>The findings showed that p16INK4a enhanced foam cells formation with increased scavenger receptors CD36 and LOX-1 expression and reduced cholesterol efflux in THP-1 macrophages. Besides, β-galactosidase activity was enhanced, and SASP factors such as IL-1α, TNF-α, and MMP9 were up-regulated. In addition, p16INK4a is also shown to induce autophagy, as well as increasing autophagy markers LC3B and p62 expression.</p><p><strong>Conclusions: </strong>This study provides insights on p16INK4a in mediating macrophages foam cells formation, cellular senescence, and foam cells formation.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The senescent marker p16INK4a enhances macrophage foam cells formation.\",\"authors\":\"Wei Sheng Siew, Yin Quan Tang, Bey Hing Goh, Wei Hsum Yap\",\"doi\":\"10.1007/s11033-024-09946-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The senescence marker p16INK4a, which constitutes part of the genome 9p21.3 cardiovascular disease (CVD) risk allele, is believed to play a role in foam cells formation. This study aims to unravel the role of p16INK4a in mediating macrophage foam cells formation, cellular senescence, and autophagy lysosomal functions.</p><p><strong>Methods: </strong>The mammalian expression plasmid pCMV-p16INK4a was used to induce p16INK4a overexpression in THP-1 macrophages. Next, wild-type and p16INK4a-overexpressed macrophages were incubated with oxidized LDL to induce foam cells formation. Lipids accumulation was evaluated using Oil-red-O staining and cholesterol efflux assay, as well as expression of scavenger receptors CD36 and LOX-1. Cellular senescence in macrophage foam cells were determined through analysis of senescence-associated β-galactosidase activity and other SASP factors expression. Meanwhile, autophagy induction was assessed through detection of autophagosome formation and LC3B/p62 markers expression.</p><p><strong>Results: </strong>The findings showed that p16INK4a enhanced foam cells formation with increased scavenger receptors CD36 and LOX-1 expression and reduced cholesterol efflux in THP-1 macrophages. Besides, β-galactosidase activity was enhanced, and SASP factors such as IL-1α, TNF-α, and MMP9 were up-regulated. In addition, p16INK4a is also shown to induce autophagy, as well as increasing autophagy markers LC3B and p62 expression.</p><p><strong>Conclusions: </strong>This study provides insights on p16INK4a in mediating macrophages foam cells formation, cellular senescence, and foam cells formation.</p>\",\"PeriodicalId\":18755,\"journal\":{\"name\":\"Molecular Biology Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-09-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Biology Reports\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s11033-024-09946-z\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Biology Reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11033-024-09946-z","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The senescent marker p16INK4a enhances macrophage foam cells formation.
Background: The senescence marker p16INK4a, which constitutes part of the genome 9p21.3 cardiovascular disease (CVD) risk allele, is believed to play a role in foam cells formation. This study aims to unravel the role of p16INK4a in mediating macrophage foam cells formation, cellular senescence, and autophagy lysosomal functions.
Methods: The mammalian expression plasmid pCMV-p16INK4a was used to induce p16INK4a overexpression in THP-1 macrophages. Next, wild-type and p16INK4a-overexpressed macrophages were incubated with oxidized LDL to induce foam cells formation. Lipids accumulation was evaluated using Oil-red-O staining and cholesterol efflux assay, as well as expression of scavenger receptors CD36 and LOX-1. Cellular senescence in macrophage foam cells were determined through analysis of senescence-associated β-galactosidase activity and other SASP factors expression. Meanwhile, autophagy induction was assessed through detection of autophagosome formation and LC3B/p62 markers expression.
Results: The findings showed that p16INK4a enhanced foam cells formation with increased scavenger receptors CD36 and LOX-1 expression and reduced cholesterol efflux in THP-1 macrophages. Besides, β-galactosidase activity was enhanced, and SASP factors such as IL-1α, TNF-α, and MMP9 were up-regulated. In addition, p16INK4a is also shown to induce autophagy, as well as increasing autophagy markers LC3B and p62 expression.
Conclusions: This study provides insights on p16INK4a in mediating macrophages foam cells formation, cellular senescence, and foam cells formation.
期刊介绍:
Molecular Biology Reports publishes original research papers and review articles that demonstrate novel molecular and cellular findings in both eukaryotes (animals, plants, algae, funghi) and prokaryotes (bacteria and archaea).The journal publishes results of both fundamental and translational research as well as new techniques that advance experimental progress in the field and presents original research papers, short communications and (mini-) reviews.