Gerthoffer William T, Singer Cherie A
Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557-0270, USA.
Respir Physiol Neurobiol. 2003 Sep 16;137(2-3):237-50. doi: 10.1016/s1569-9048(03)00150-2.
Mitogen-activated protein kinases (MAPK) are important components of signaling modules activated by neurotransmitters, cytokines, and growth factors, as well as chemical and mechanical stressors. In the airway, these external signals produce acute responses that modify smooth muscle contraction and may also induce chronic responses that modify airway structure. Both acute and chronic events in airway remodeling result from altered expression of multiple genes encoding protein mediators of cell-cell signaling, extracellular matrix remodeling, cell cycle control and intracellular signaling pathways. This review will focus on inflammatory and growth factor mediators of cell-cell signaling regulated by the ERK and p38 MAPK pathways in airway smooth muscle (ASM). These signaling mediators affect ASM tissue mechanics, cell migration, and gene expression patterns in a paracrine and autocrine fashion, although the relative importance of each MAPK pathway varies with the stimulus. These events thereby contribute to normal airway function and participate in pathological changes in ASM that accompany symptoms of asthma.
丝裂原活化蛋白激酶（MAPK）是由神经递质、细胞因子、生长因子以及化学和机械应激源激活的信号模块的重要组成部分。在气道中，这些外部信号会产生急性反应，改变平滑肌收缩，也可能诱导改变气道结构的慢性反应。气道重塑中的急性和慢性事件均源于多种基因表达的改变，这些基因编码细胞间信号传导、细胞外基质重塑、细胞周期控制和细胞内信号通路的蛋白质介质。本综述将聚焦于气道平滑肌（ASM）中由ERK和p38 MAPK通路调节的细胞间信号传导的炎症和生长因子介质。这些信号介质以旁分泌和自分泌方式影响ASM组织力学、细胞迁移和基因表达模式，尽管每种MAPK通路的相对重要性因刺激而异。这些事件从而有助于正常气道功能，并参与伴随哮喘症状的ASM病理变化。
