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dc.contributor.authorAfroz, Rizwana
dc.contributor.authorZhou, Ying
dc.contributor.authorLittle, Peter J
dc.contributor.authorXu, Suowen
dc.contributor.authorMohamed, Raafat
dc.contributor.authorStow, Jennifer
dc.contributor.authorKamato, Danielle
dc.date.accessioned2022-02-18T00:54:47Z
dc.date.available2022-02-18T00:54:47Z
dc.date.issued2020
dc.identifier.issn2575-9108
dc.identifier.doi10.1021/acsptsci.9b00113
dc.identifier.urihttp://hdl.handle.net/10072/412451
dc.description.abstractAtherosclerosis begins in the vessel wall with the retention of low density lipoproteins to modified proteoglycans with hyperelongated glycosaminoglycan (GAG) chains. Bacterial infections produce endotoxins such as lipopolysaccharide that exacerbate the outcome of atherosclerosis by generating a heightened state of inflammation. Lipopolysaccharide (LPS) via its toll-like receptor (TLR) is well-known for its role in mediating an inflammatory response in the body. Emerging evidence demonstrates that TLRs are involved in regulating vascular functions. In this study we sought to investigate the role of LPS in proteoglycan modification and GAG chain elongation, and we hypothesize that LPS will signal via Smad2 dependent pathways to regulate GAG chain elongation. The in vitro model used human aortic vascular smooth muscle cells. GAG gene expression was assessed by quantitative real-time polymerase chain reaction. Western blotting was performed using whole-cell protein lysates to assess the signaling pathway. LPS via TLR4 stimulates the expression of GAG synthesizing enzymes to an equal extent to traditional cardiovascular agonists. LPS phosphorylates the Smad2 linker region via TAK-1/MAPK dependent pathways which correlated with genes associated with GAG chain initiation and elongation. The well-characterized role of LPS in inflammation and our data on GAG gene expression demonstrates that GAG chain elongation is the earliest marker of the inflammatory cascade in atherosclerosis development.
dc.description.peerreviewedYes
dc.languageen
dc.publisherAmerican Chemical Society (ACS)
dc.relation.ispartofpagefrom524
dc.relation.ispartofpageto534
dc.relation.ispartofissue3
dc.relation.ispartofjournalACS Pharmacology & Translational Science
dc.relation.ispartofvolume3
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchMedical biochemistry and metabolomics
dc.subject.fieldofresearchcode3214
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3205
dc.titleToll-like Receptor 4 Stimulates Gene Expression via Smad2 Linker Region Phosphorylation in Vascular Smooth Muscle Cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationAfroz, R; Zhou, Y; Little, PJ; Xu, S; Mohamed, R; Stow, J; Kamato, D, Toll-like Receptor 4 Stimulates Gene Expression via Smad2 Linker Region Phosphorylation in Vascular Smooth Muscle Cells, ACS Pharmacology & Translational Science, 2020, 3 (3), pp. 524-534
dc.date.updated2022-02-17T05:16:33Z
gro.hasfulltextNo Full Text
gro.griffith.authorAfroz, Rizwana
gro.griffith.authorKamato, Danielle


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