title: Heat shock protein 60 stimulates the migration of vascular smooth muscle cells via Toll-like receptor 4 and ERK MAPK activation.
abstract: Accumulating evidence indicates that heat shock protein (HSP) 60 is strongly associated with the pathology of atherosclerosis (AS). However, the precise mechanisms by which HSP60 promotes atherosclerosis remain unclear. In the present study, we found that HSP60 mRNA and protein expression levels in the thoracic aorta are enhanced not only in a mouse model of AS but also in high-fat diet (HFD) mice. HSP60 expression and secretion was activated by platelet-derived growth factor-BB (PDGF-BB) and interleukin (IL)-8 in both human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs). HSP60 was found to induce VSMC migration, and exposure to HSP60 activated ERK MAPK signaling. U0126, an inhibitor of ERK, reduced VSMC migration. The HSP60-stimulated VSMCs were found to express TLR4 mRNA but not TLR2 mRNA. Knockdown of TLR4 by siRNA reduced HSP60-induced VSMC migration and HSP60-induced ERK activation. Finally, HSP60 induced IL-8 secretion in VSMCs. Together these results suggest that HSP60 is involved in the stimulation of VSMC migration, via TLR4 and ERK MAPK activation. Meanwhile, activation of HSP60 is one of the most powerful methods of sending a 'danger signal' to the immune system to generate IL-8, which assists in the management of an infection or disease.
authors.affiliation: Liaoning Provincial Core Lab of Medical Molecular Biology, Dalian Medical University, Dalian, 116044, China.|Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Chenxu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Xuge
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Liaoning Provincial Core Lab of Medical Molecular Biology, Dalian Medical University, Dalian, 116044, China.|Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Yuanhua
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Liaoning Provincial Core Lab of Medical Molecular Biology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wei
authors.affiliation: Liaoning Provincial Core Lab of Medical Molecular Biology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Minli
authors.initials: M
authors.lastname: Jin
authors.affiliation: Research Institute of Pharmaceutical Sciences, Musashino University, Nishitokyo, Tokyo, 2028585, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kohama
authors.affiliation: Liaoning Provincial Core Lab of Medical Molecular Biology, Dalian Medical University, Dalian, 116044, China.|Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D051379:Mice; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D018834:Chaperonin 60; D016209:Interleukin-8; D051197:Toll-Like Receptor 4; D048049:Extracellular Signal-Regulated MAP Kinases