Zic family member 3 attenuates oxidative stress-induced vascular smooth muscle cell apoptosis in patients with chronic kidney disease

作者全名："Gao, Jianya; Liu, Lei; Wu, Zecheng; Gan, Hua"

作者地址："[Gao, Jianya; Liu, Lei; Gan, Hua] Chongqing Med Univ, Affiliated Hosp 1, Dept Nephrol, Chongqing 400016, Peoples R China; [Gao, Jianya; Liu, Lei; Wu, Zecheng] Chongqing Univ, Three Gorges Hosp, Dept Nephrol, Chongqing 404100, Peoples R China"

通信作者："Gan, H (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Nephrol, Chongqing 400016, Peoples R China."

来源：TISSUE & CELL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001137257600001

JCR分区：Q1

影响因子：2.7

年份：2024

卷号：86

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：ZIC3; Chronic kidney disease; Neointimal hyperplasia; Vascular smooth muscle cells

摘要："Neointimal hyperplasia is reportedly essential for arteriovenous fistulas (AVF) in patients undergoing hemodialysis. Oxidative stress is vital in the progression of uremic venous intimal hyperplasia. Studies have suggested that zinc ions obstruct vascular calcification in patients with chronic kidney disease (CKD). Recent studies have shown that the zinc finger protein, Zic family member 3 (ZIC3), is crucial for the earliest cardiovascular pro-genitors. ZIC3 mutations are associated with congenital heart disease. However, the mechanism of action of ZIC3 in vascular intimal hyperplasia in CKD remains unelucidated. Venous specimens were collected during primary AVF surgery and traumatic amputation, and serum samples were collected from patients with CKD and healthy controls. Mouse vascular smooth muscle cells (VSMCs) were treated with hydrogen peroxide (H2O2) to clarify the role of ZIC3 in CKD. ZIC3 expression was reduced in the veins of patients with uremia and the serum of those with CKD. Zic3 and Bcl2 levels were significantly decreased in mouse VSMCs treated with H2O2 & sdot;H2O2 inhibited mouse VSMC activity, upregulated Bax, and cleaved caspase 3 expression. Following Zic3 overexpression, Bcl2 expression level and cell viability were elevated, whereas Bax and cleaved caspase 3 expression levels were downregulated. In contrast, Zic3 knockdown yielded the opposite results. Therefore, ZIC3 could be a new therapeutic target in venous neointimal hyperplasia of CKD."

基金机构：Faculty of the Department of Nephrology of the First Hospital of Chongqing Medical University; Chongqing University Three Gorges Hospital

基金资助正文：This research work was supported by the faculty of the Department of Nephrology of the First Hospital of Chongqing Medical University and Chongqing University Three Gorges Hospital.