Li Te-Mao, Liu Shan-Chi, Huang Ya-Hsin, Huang Chien-Chung, Hsu Chin-Jung, Tsai Chun-Hao, Wang Shih-Wei, Tang Chih-Hsin
School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan.
Int J Mol Sci. 2017 Apr 27;18(5):920. doi: 10.3390/ijms18050920.
YKL-40, also known as human cartilage glycoprotein-39 or chitinase-3-like-1, is a pro-inflammatory protein that is highly expressed in rheumatoid arthritis (RA) patients. Angiogenesis is a critical step in the pathogenesis of RA, promoting the infiltration of inflammatory cells into joints and providing oxygen and nutrients to RA pannus. In this study, we examined the effects of YKL-40 in the production of the pro-inflammatory cytokine interleukin-18 (IL-18), and the stimulation of angiogenesis and accumulation of osteoblasts. We observed that YKL-40 induces IL-18 production in osteoblasts and thereby stimulates angiogenesis of endothelial progenitor cells (EPCs). We found that this process occurs through the suppression of miR-590-3p via the focal adhesion kinase (FAK)/PI3K/Akt signaling pathway. YKL-40 inhibition reduced angiogenesis in in vivo models of angiogenesis: the chick embryo chorioallantoic membrane (CAM) and Matrigel plug models. We report that YKL-40 stimulates IL-18 expression in osteoblasts and facilitates EPC angiogenesis.
YKL-40，也被称为人软骨糖蛋白-39或几丁质酶-3样蛋白-1，是一种在类风湿性关节炎（RA）患者中高表达的促炎蛋白。血管生成是RA发病机制中的关键步骤，它促进炎症细胞浸润到关节中，并为RA血管翳提供氧气和营养物质。在本研究中，我们检测了YKL-40在促炎细胞因子白细胞介素-18（IL-18）产生、血管生成刺激和成骨细胞积累方面的作用。我们观察到YKL-40诱导成骨细胞产生IL-18，从而刺激内皮祖细胞（EPCs）的血管生成。我们发现这个过程是通过粘着斑激酶（FAK）/PI3K/Akt信号通路抑制miR-590-3p来实现的。YKL-40抑制作用降低了血管生成体内模型中的血管生成：鸡胚绒毛尿囊膜（CAM）模型和基质胶栓塞模型。我们报道YKL-40刺激成骨细胞中IL-18的表达并促进EPC血管生成。
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