Recombinant heat shock protein 60 stimulates the migration of vascular smooth muscle cells via the Toll-like receptor 4 and ERK MAPK activation

【摘要】：Atherosclerosis is a multifactorial disease for which a number of different pathogenicmechanisms have been proposed. Growing evidence indicates that heat shock protein(HSP) 60 has a strong association with atherosclerosis. However, the precise mechanism(s)by which HSP60 promotes atherosclerosis remains unclear. In the present study, we foundthat the HSP60 mRNA and protein expression levels in thoracic aortas significantly increasedin high-fat diet(H.F.D.) and in atherosclerosis(AS) mice. HSP60 expression was activatedby Platelet-derived growth factor-BB(PDGF-BB) and interleukin(IL)-8. HSP60 inducedvascular smooth muscle cells(VSMCs) migration. Exposure to HSP60 rapidly activatedERK MAPK within 10 minutes. U0126, which is an inhibitor of ERK, reduced the numberof migrating VSMCs. The VSMCs were demonstrated to express TLR4 mRNA but notTLR2. TLR4 siRNA reduced HSP60-induced VSMC migration and HSP60-induced ERK activation.HSP60 induces IL-8 secretion in VSMC. Together these results indicate that HSP60 may stimulate the migration of VSMCs via TLR4 and ERK MAPK activation. Meanwhile, activationof HSP60 is one of the most powerful methods of sending a ‘danger signal' tothe immune system to generate IL-8, which assists the organism's ability to manage aninfection or disease.