title: Induction of DKK1 by ox-LDL negatively regulates intracellular lipid accumulation in macrophages.
abstract: Dickkopf1 (DKK1), a canonical Wnt/β-catenin pathway antagonist, is closely associated with cardiovascular disease and adipogenesis. We performed an in vitro study to determine whether oxidized low-density lipoprotein (ox-LDL) increased the expression of DKK1 in macrophages and whether β-catenin and liver X receptor α (LXRα) were involved in this regulation. Induction of DKK1 expression by ox-LDL decreased the level of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) via a Wnt/β-catenin pathway and increased ATP-binding cassette transporter A/G1 (ABCA/G1) levels via a signal transducer and activator of transcription 3 (STAT3) pathway. Lower LOX-1 and higher ABCA/G1 levels inhibited cholesterol loading in macrophages. In conclusion, ox-LDL may induce DKK1 expression in macrophages to inhibit the accumulation of lipids through a mechanism that involves downregulation of LOX-1-mediated lipid uptake and upregulation of ABCA/G1-dependent cholesterol efflux.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ge
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong Province, China. Electronic address: daixh@vip.sina.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism*; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C495137:OLR1 protein, human; D057093:Orphan Nuclear Receptors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D002784:Cholesterol
keywords: ATP-binding cassette transporter A/G1; Dickkopf1; Lectin-like oxidized low-density lipoprotein receptor-1; Lipid metabolism