Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.
Hebei key Laboratory of Chinese Medicine Research on Cardio-cerebrovascular Disease, Shijiazhuang, Hebei, China.
Ren Fail. 2021 Dec;43(1):566-576. doi: 10.1080/0886022X.2021.1902822.
This study sought to investigate the effect of local expression of galectin-3 in the development of stenotic arteriovenous fistula (AVF).
We collected stenotic venous tissues, adjacent nonstenotic venous tissues, and blood samples from end-stage renal disease (ESRD) patients with AVF stenosis, while normal venous tissues and blood samples were collected from ESRD patients before AVF creation as controls. Also blood samples were collected from ESRD patients with nonstenosis functional AVF. Galectin-3, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-9 (MMP-9), and α-SMA expression in the venous tissues were examined by immunohistochemistry, and the ERK1/2 pathway activity in the intima was accessed by western blot. Serum galectin-3 level was measured by ELISA. Thereafter, human pulmonary arterial smooth muscle cells (HPASMCs) were cultured , and the interaction between Galectin-3 and ERK1/2 pathway in HPASMCs was estimated by western blot.
ESRD patients with stenotic AVF had a significant higher serum galectin-3 level than normal controls, and patients with non-stenotic functional AVF. The expression levels of galectin-3, phosphorylated ERK1/2, PCNA, MMP-9, and α-SMA in the stenotic venous tissues were higher than that in the normal venous tissues or the adjacent nonstenotic AVF venous tissues. Correlation analysis showed that the expression of galectin-3 of the neointima was positively correlated with PCNA and α-SMA in the stenotic AVF venous tissues. In HPASMCs, galectin-3 can increase the activity of phosphorylated ERK1/2 and promote the expression of α-SMA.
In the stenotic AVF of ESRD patients, expression of the galectin-3 was significantly increased, showing a positive relation with neointima development.
本研究旨在探讨局部表达半乳糖凝集素-3（galectin-3）在狭窄性动静脉瘘（AVF）发展中的作用。
我们收集了终末期肾病（ESRD）患者狭窄性 AVF 静脉组织、相邻非狭窄性静脉组织和血液样本，同时收集了 ESRD 患者 AVF 形成前的正常静脉组织和血液样本作为对照。还收集了 ESRD 患者非狭窄性功能 AVF 的血液样本。通过免疫组织化学检测静脉组织中 galectin-3、增殖细胞核抗原（PCNA）、基质金属蛋白酶-9（MMP-9）和α-SMA 的表达，通过 Western blot 检测内膜中 ERK1/2 通路的活性。通过 ELISA 测定血清 galectin-3 水平。然后，培养人肺动脉平滑肌细胞（HPASMCs），通过 Western blot 评估 Galectin-3 与 HPASMCs 中 ERK1/2 通路的相互作用。
狭窄性 AVF 的 ESRD 患者血清 galectin-3 水平明显高于正常对照组和非狭窄性功能 AVF 患者。狭窄性静脉组织中 galectin-3、磷酸化 ERK1/2、PCNA、MMP-9 和α-SMA 的表达水平均高于正常静脉组织或相邻非狭窄性 AVF 静脉组织。相关性分析显示，狭窄性 AVF 静脉组织中新生内膜的 galectin-3 表达与 PCNA 和α-SMA 呈正相关。在 HPASMCs 中，galectin-3 可增加磷酸化 ERK1/2 的活性并促进α-SMA 的表达。
在 ESRD 患者狭窄性 AVF 中，galectin-3 的表达明显增加，与新生内膜的发展呈正相关。
