title: Galectin-3-induced oxidized low-density lipoprotein promotes the phenotypic transformation of vascular smooth muscle cells.
abstract: Oxidized low-density lipoprotein (oxLDL) is involved in the pathological phenotypic transformation of vascular smooth muscle cells in atherosclerosis. Galectin‑3 also has an important role in atherosclerosis. However, little is currently known regarding the effects of galectin‑3 on the oxLDL‑induced phenotypic transformation of vascular smooth muscle cells. In the present study, primary culture human umbilical vascular smooth muscle cells were treated with various oxLDL concentrations (0‑50 µg/ml) for 72 h, and phenotypic changes were subsequently recorded. The results of the present study suggested that oxLDL increases the expression levels of galectin‑3, and induces the phenotypic transformation of vascular smooth muscle cells. The oxLDL‑induced cells exhibited increased expression levels of osteopontin, a smooth muscle synthetic protein, and calponin and α‑actin, smooth muscle contractile proteins. The oxLDL‑induced changes in cellular phenotype were associated with increased migration, proliferation, and phagocytosis. Concordant with these results, oxLDL‑treated smooth muscle cells exhibited activation of canonical Wnt signaling, as determined by an increase in the protein expression levels of β‑catenin. Silencing of galectin‑3 by small interfering RNA reversed the phenotypic transformation and functional changes observed in the oxLDL‑treated cells, suggesting these changes were dependent on the activation of galectin‑3. In addition, galectin‑3 knockdown decreased the protein expression levels of β‑catenin in both the cytoplasm and nucleus; however, the mRNA expression levels of β‑catenin remained unchanged. These results suggest that galectin‑3 is responsible for the phenotypic transformation of human umbilical vascular smooth muscle cells, and the canonical Wnt/β-catenin signaling pathway may be involved in this process.
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, P.R. China.
authors.forename: Kan
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, P.R. China.
authors.forename: Jiatian
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, P.R. China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, P.R. China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Cardiology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, P.R. China.
authors.forename: Changqian
authors.initials: C
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D001798:Blood Proteins; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D037502:Galectin 3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D037161:Galectins; D005786:Gene Expression Regulation; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism; D000096985:Calponins
chemical_list: D000199:Actins; D001798:Blood Proteins; D002135:Calcium-Binding Proteins; D037502:Galectin 3; D037161:Galectins; D008077:Lipoproteins, LDL; D008840:Microfilament Proteins; D053495:Osteopontin; D034741:RNA, Small Interfering; D051176:beta Catenin; D000096985:Calponins; C495270:CTNNB1 protein, human; C428445:LGALS3 protein, human; C099252:oxidized low density lipoprotein