Department of Vascular Surgery, Clinical Division of Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
Mol Biol Rep. 2013 Apr;40(4):2939-46. doi: 10.1007/s11033-012-2309-1. Epub 2012 Dec 1.
A chemokine-like factor 1 (CKLF1) is a recently discovered chemokine with broad-spectrum biological functions in inflammation and autoimmune diseases. C19 as a CKLF1's C-terminal peptide has been reported to exert inhibitory effects in a variety of diseases. However, the roles of CKLF1 and C19 on vascular smooth muscle cell (VSMC) migration and neointima formation still remain elusive. The effects of CKLF1 and C19 on VSMC migration and neointimal formation were investigated in cultured VSMCs and balloon-injured rat carotid arteries based on techniques including adenovirus-induced CKLF1 overexpression, gel based perivascular administration of C19, Boyden chamber, scratch-wound assay, real-time PCR, western blot and immunohistochemical analysis. CKLF1 was noticed to accumulate preferentially in neointima after the injury and colocalize with VSMCs. Luminal delivery of CKLF1 adenovirus to arteries exacerbated intimal thickening while perivascular administration of C19 to injured arteries attenuated this problem. In cultured primary VSMCs, CKLF1 overexpression up-regulated VSMC migration, which was down-regulated by C19. These data suggest that CKLF1 has a pivotal role in intimal hyperplasia by mediating VSMC migration. C19 was demonstrated to inhibit CKLF1-mediatated chemotaxis and restenosis. Thus further studies on C19 may provide a new treatment perspective for atherosclerosis and post-angioplasty restenosis.
趋化因子样因子 1（CKLF1）是一种新发现的趋化因子，在炎症和自身免疫性疾病中有广泛的生物学功能。C19 作为 CKLF1 的 C 端肽段，已被报道在多种疾病中发挥抑制作用。然而，CKLF1 和 C19 对血管平滑肌细胞（VSMC）迁移和新生内膜形成的作用仍不清楚。本研究通过腺病毒诱导 CKLF1 过表达、基于凝胶的血管周围给予 C19、Boyden 室、划痕实验、实时 PCR、Western blot 和免疫组织化学分析等技术，在培养的 VSMC 和球囊损伤大鼠颈动脉中研究了 CKLF1 和 C19 对 VSMC 迁移和新生内膜形成的影响。结果发现 CKLF1 在损伤后优先积聚在新生内膜中，并与 VSMC 共定位。将 CKLF1 腺病毒递送至动脉管腔会加剧内膜增厚，而将 C19 给予损伤的动脉周围则可减轻这一问题。在培养的原代 VSMC 中，CKLF1 过表达上调了 VSMC 的迁移，而 C19 则下调了这种迁移。这些数据表明，CKLF1 通过介导 VSMC 迁移在血管内膜增生中起关键作用。C19 被证明可以抑制 CKLF1 介导的趋化作用和再狭窄。因此，进一步研究 C19 可能为动脉粥样硬化和血管成形术后再狭窄提供新的治疗视角。
