Downregulation of smooth muscle alpha-actin expression by bacterial lipopolysaccharide.
Downregulation of smooth muscle alpha-actin expression by bacterial lipopolysaccharide.
复制标题
细菌脂多糖下调平滑肌α-肌动蛋白表达。
DOI：
10.1016/j.cardiores.2007.01.011
复制
发表时间：
2007
影响因子：
10.8
通讯作者：
Dulin,NickolaiO
中科院分区：
文献类型：
--
作者：
Sandbo,Nathan;Taurin,Sebastien;Yau,DouglasM;Kregel,Steven;Mitchell,Richard;Dulin,NickolaiO
目的：平滑肌α-肌动蛋白（SMA）是血管平滑肌细胞（VSMC）特有的一种细胞骨架蛋白，有助于细胞收缩和迁移。细菌脂多糖（LPS）是继发于感染的败血性休克的主要介质，已知其直接影响VSMC。方法：采用体外培养的人主动脉、人冠状动脉和大鼠主动脉血管平滑肌细胞（VSMC），观察内毒素（LPS）对平滑肌肌动蛋白（SMA）表达的影响。这与LPS处理后VSMC迁移减少平行。LPS对SMA的下调不是ET 1或TGF-β受体信号传导改变的结果，也不是由经典（LPS）机制介导的，如产生胰高血糖素或一氧化氮，或分泌其他内分泌因子。在分子水平上，由于SMA mRNA水平和SMA启动子活性均被LPS抑制，因此LPS对SMA表达的下调发生在转录水平。SMA启动子主要受两种主要调控元件-血清反应因子（SRF）激活的CArG盒和TGF-β控制元件（TCE）控制。LPS不影响SRF的活性，但它有力地抑制了基础和诱导TCE activation.Conclusion：我们首次表明，LPS可能通过抑制SMA启动子上的TCE元件来减弱SMA在VSMC中的转录和蛋白表达。
Objective: Smooth muscle α-actin (SMA) is a cytoskeletal protein characteristic to vascular smooth muscle cells (VSMC), and it serves to facilitate cell contraction and migration. Bacterial lipopolysaccharide (LPS), a major mediator of septic shock secondary to infection, is known to directly affect VSMC. The objective of this study was to investigate the effect of LPS on the expression levels of SMA in VSMC.Methods: This study was performed on cultured VSMC derived from human aorta, human coronary artery, or rat aorta.Results: We show that SMA expression in VSMC, induced by endothelin-1 (ET1) or transforming growth factor-β (TGF-β), is potently inhibited by a LPS. This parallels a decreased migration of VSMC after LPS treatment. Downregulation of SMA by LPS is not a result of altered signaling of ET1 or TGF-β receptors, and it is not mediated by canonical (for LPS) mechanisms, such as production of prostaglandins or nitric oxide, or secretion of other endocrine factors. On a molecular level, downregulation of SMA expression by LPS occurs at the level of transcription, as both SMA mRNA levels and SMA promoter activity are inhibited by LPS. The SMA promoter is controlled largely by two major regulatory elements–CArG boxes activated by serum response factor (SRF), and TGF-β control elements (TCE). LPS does not affect the activity of SRF, but it potently inhibits both basal and inducible TCE activation.Conclusion: We show for the first time that LPS attenuates SMA transcription and protein expression in VSMC likely through inhibition of a TCE element on the SMA promoter.