The p38 mitogen-activated protein kinases modulate endothelial cell survival and tissue repair
The p38 mitogen-activated protein kinases modulate endothelial cell survival and tissue repair
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DOI：
10.1007/s00011-011-0405-7
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发表时间：
2012-03-01
影响因子：
6.7
通讯作者：
Liu, Xiangde
中科院分区：
文献类型：
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作者：
Kanaji, Nobuhiro;Nelson, Amy;Liu, Xiangde
本研究旨在探讨p38 MAPK在调节人肺动脉内皮细胞（HPAECs）存活和组织修复功能中的作用。用IL-1 β（0.5或2 ng/ml）或p38抑制剂（SB 203580或SB 220025，各5 μ M）处理细胞。还用50 nM siRNA转染细胞。使用ImageJ软件测量细胞长度。采用胶原凝胶收缩法和伤口闭合法检测HPAECs的组织修复功能，IL-1 β激活p38 MAPK，诱导HPAECs形态学改变。p38抑制剂进一步增强IL-1 β诱导的细胞形态学变化，防止细胞死亡，并增强胶原凝胶收缩。抑制p38 α、γ或δ，但不抑制p38 β，导致细胞形态学改变，并且通过siRNA抑制任何一种p38同种型增加细胞存活。抑制p38 α或δ增强的凝胶收缩。虽然p38 α抑制刺激细胞迁移，抑制其余三种亚型抑制细胞迁移。核因子p65-siRNA可阻断IL-1 β诱导的内皮细胞形态学改变，但不影响p38 MAPK诱导的内皮细胞形态学改变，提示p38 MAPK可能通过p65非依赖性途径负性调节内皮细胞的组织修复功能。
This study is designed to investigate the role of p38 MAPK in modulating human pulmonary artery endothelial cells (HPAECs) survival and tissue repair functions.HPAECs (passage 8-12) were used for all experiments. Cells were treated with IL-1 beta (0.5 or 2 ng/ml) or p38 inhibitor (SB203580 or SB220025, 5 mu M each). Cells were also transfected with 50 nM siRNAs. Cell length was measured using ImageJ software. Collagen gel contraction and wound close assay were performed to evaluate tissue repair functions.IL-1 beta activated p38 MAPK and induced morphologic change of HPAECs. The p38 inhibitors further augmented IL-1 beta-induced cell morphologic change, prevented cell death, and augmented collagen gel contraction. Suppression of p38 alpha, gamma, or delta, but not p38 beta resulted in cell morphologic alteration, and suppressing any one of p38 isoforms by siRNAs increased cell survival. Suppression of p38 alpha or delta augmented gel contraction. While p38 alpha suppression stimulated cell migration, suppressing the rest of three isoforms inhibit cell migration. Nuclear factor p65-siRNA blocked IL-1 beta-induced cell morphologic change, but did not affect p38 inhibitor-induced change.These findings suggest that p38 MAPK may negatively modulate tissue repair functions of endothelial cells via p65 independent pathway.