Adiponectin enhances intercellular adhesion molecule-1 expression and promotes monocyte adhesion in human synovial fibroblasts.
Adiponectin enhances intercellular adhesion molecule-1 expression and promotes monocyte adhesion in human synovial fibroblasts.
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DOI：
10.1371/journal.pone.0092741
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tang CH
中科院分区：
文献类型：
--
作者：
Chen HT;Tsou HK;Chen JC;Shih JM;Chen YJ;Tang CH
脂联素是一种主要由分化脂肪细胞分泌的蛋白质激素，参与能量稳态。骨关节炎（OA）患者的滑液中脂联素表达显着升高。细胞间粘附分子-1 (ICAM-1) 是 OA 发病过程中介导单核细胞粘附和浸润的重要粘附分子。通过 qPCR、流式细胞术和蛋白质印迹法检测脂联素诱导的人 OA 滑膜成纤维细胞 (OASF) 中 ICAM-1 的表达。通过用抑制剂预处理或用siRNA转染来研究细胞内信号通路。单核细胞 THP-1 细胞系用于 OASF 的粘附测定。用脂联素刺激 OASF 诱导 ICAM-1 表达。用 AMP 激活蛋白激酶 (AMPK) 抑制剂（AraA 和化合物 C）预处理或用针对 AMPKα1 和两个 AMPK 上游激活剂肝激酶 B1 (LKB1) 和钙调蛋白依赖性蛋白激酶 II (CaMKII) 的 siRNA 转染可减少脂联素诱导的 ICAM-1 表达。用脂联素刺激 OASF 会增加 LKB1、CaMKII、AMPK 和 c-Jun 的磷酸化，导致 c-Jun 与 ICAM-1 启动子的 AP-1 元件结合。此外，脂联素诱导的 LKB1/CaMKII、AMPK 和 AP-1 通路激活增加了单核细胞与 OASF 单层的粘附。我们的结果表明，脂联素通过 LKB1/CaMKII、AMPK、c-Jun 和 AP-1 信号通路增加人 OASF 中 ICAM-1 的表达。脂联素诱导的 ICAM-1 表达促进单核细胞与人 OASF 的粘附。这些发现可能有助于更好地了解 OA 的发病机制，并可以利用这些知识来设计新的治疗策略。
Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and is involved in energy homeostasis. Adiponectin expression is significantly high in the synovial fluid of patients with osteoarthritis (OA). Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule that mediates monocyte adhesion and infiltration during OA pathogenesis. Adiponectin-induced expression of ICAM-1 in human OA synovial fibroblasts (OASFs) was examined by using qPCR, flow cytometry and western blotting. The intracellular signaling pathways were investigated by pretreated with inhibitors or transfection with siRNA. The monocyte THP-1 cell line was used for an adhesion assay with OASFs. Stimulation of OASFs with adiponectin induced ICAM-1 expression. Pretreatment with AMP-activated protein kinase (AMPK) inhibitors (AraA and compound C) or transfection with siRNA against AMPKα1 and two AMPK upstream activator- liver kinase B1 (LKB1) and calmodulin-dependent protein kinase II (CaMKII) diminished the adiponectin-induced ICAM-1 expression. Stimulation of OASFs with adiponectin increased phosphorylation of LKB1, CaMKII, AMPK, and c-Jun, resulting in c-Jun binding to AP-1 element of ICAM-1 promoter. In addition, adiponectin-induced activation of the LKB1/CaMKII, AMPK, and AP-1 pathway increased the adhesion of monocytes to the OASF monolayer. Our results suggest that adiponectin increases ICAM-1 expression in human OASFs via the LKB1/CaMKII, AMPK, c-Jun, and AP-1 signaling pathway. Adiponectin-induced ICAM-1 expression promoted the adhesion of monocytes to human OASFs. These findings may provide a better understanding of the pathogenesis of OA and can utilize this knowledge to design a new therapeutic strategy.
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影响因子：
4.9
作者：
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通讯作者：
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4.9
作者：
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影响因子：
6
作者：
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影响因子：
4.4
作者：
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通讯作者：
Mueller-Ladner, Ulf
影响因子：
3.9
作者：
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通讯作者：
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