Connective tissue growth factor is correlated with peritoneal lymphangiogenesis
Connective tissue growth factor is correlated with peritoneal lymphangiogenesis
复制标题
结缔组织生长因子与腹膜淋巴管生成相关
DOI：
10.1038/s41598-019-48699-9
复制
发表时间：
2019
影响因子：
4.6
通讯作者：
Ito Yasuhiko
中科院分区：
文献类型：
--
作者：
Kinashi Hiroshi;Toda Naohiro;Sun Ting;Nguyen Tri Q.;Suzuki Yasuhiro;Katsuno Takayuki;Yokoi Hideki;Aten Jan;Mizuno Masashi;Maruyama Shoichi;Yanagita Motoko;Goldschmeding Roel;Ito Yasuhiko
腹膜腔内的淋巴吸收可能导致腹膜透析（PD）超滤失败。淋巴管在PD相关腹膜纤维化期间形成。结缔组织生长因子（CTGF，也称为CCN 2）是纤维化组织重塑的重要决定因素，但对其可能参与淋巴管生成知之甚少。在这项研究中，我们探讨了CTGF和腹膜淋巴管生成的关系。血管内皮生长因子-C（VEGF-C），一种主要的淋巴管生成生长因子，与人PD流出液中CTGF浓度呈正相关。CTGF的表达与淋巴管标志物和VEGF-C的表达呈正相关。我们发现，在用转化生长因子-β1（TGF-β1）处理的培养的人腹膜间皮细胞（HPMCs）中，CTGF的增加与VEGF-C的增加呈正相关。膈是腹膜淋巴吸收的中心。在葡萄糖酸氯己定（CG）诱导的大鼠血管纤维化模型中，CTGF的表达与VEGF-C的表达和纤维化相关。此外，CTGF基因缺失减少VEGF-C表达和腹膜淋巴管生成的小鼠CG模型。CTGF的抑制也减少了TGF-β1处理的HPMC中VEGF-C的上调。我们的研究结果表明，CTGF和PD相关的淋巴管生成之间的密切关系。
Lymphatic absorption in the peritoneal cavity may contribute to ultrafiltration failure in peritoneal dialysis (PD). Lymphatic vessels develop during PD-related peritoneal fibrosis. Connective tissue growth factor (CTGF, also called CCN2) is an important determinant of fibrotic tissue remodeling, but little is known about its possible involvement in lymphangiogenesis. In this study, we investigated the relationship between CTGF and peritoneal lymphangiogenesis. A positive correlation was observed between vascular endothelial growth factor-C (VEGF-C), a major lymphangiogenic growth factor, and the CTGF concentration in human PD effluents. CTGF expression was positively correlated with expression of lymphatic markers and VEGF-C in human peritoneal biopsies. We found a positive correlation between the increase in CTGF and the increase in VEGF-C in cultured human peritoneal mesothelial cells (HPMCs) treated with transforming growth factor-β1 (TGF-β1). The diaphragm is a central player in peritoneal lymphatic absorption. CTGF expression was also correlated with expression of VEGF-C and lymphatics in a rat diaphragmatic fibrosis model induced by chlorhexidine gluconate (CG). Furthermore, CTGF gene deletion reduced VEGF-C expression and peritoneal lymphangiogenesis in the mouse CG model. Inhibition of CTGF also reduced VEGF-C upregulation in HPMCs treated with TGF-β1. Our results suggest a close relationship between CTGF and PD-associated lymphangiogenesis.