Role of Sp1/ABCA1 signaling pathway in uremic atherosclerosis and its regulatory mechanism

Huang Ningchuan; Ma Hui; Ma Peng

doi:10.13406/j.cnki.cyxb.003661

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Role of Sp1/ABCA1 signaling pathway in uremic atherosclerosis and its regulatory mechanism

Basic research | 更新时间：2025-10-22

- Role of Sp1/ABCA1 signaling pathway in uremic atherosclerosis and its regulatory mechanism
- Journal of Chongqing Medical University Vol. 50, Issue 6, Pages: 808-814(2025)
- 作者机构：
  
  贵州中医药大学第一附属医院肾内科，贵阳 550001
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003661
  CLC： R692
- Received：13 April 2023，
  
  Revised：2023-08-29，
  
  Accepted：11 September 2023，
  
  Published：28 June 2025
- 稿件说明：
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黄宁川,马辉,马鹏.Sp1/ABCA1信号通路在尿毒症动脉粥样硬化中的作用及其调节机制[J].重庆医科大学学报,2025,50(6):808-814.

Huang Ningchuan,Ma Hui,Ma Peng.Role of Sp1/ABCA1 signaling pathway in uremic atherosclerosis and its regulatory mechanism[J].Journal of Chongqing Medical University,2025,50(6):808-814.
黄宁川,马辉,马鹏.Sp1/ABCA1信号通路在尿毒症动脉粥样硬化中的作用及其调节机制[J].重庆医科大学学报,2025,50(6):808-814. DOI： 10.13406/j.cnki.cyxb.003661.

Huang Ningchuan,Ma Hui,Ma Peng.Role of Sp1/ABCA1 signaling pathway in uremic atherosclerosis and its regulatory mechanism[J].Journal of Chongqing Medical University,2025,50(6):808-814. DOI： 10.13406/j.cnki.cyxb.003661.

摘要

目的

探讨特异性蛋白1（specificity protein 1，Sp1）/三磷酸腺苷结合盒转运蛋白A1（adenosine triphosphate-binding cassette transporter A1，ABCA1）信号通路在尿毒症动脉粥样硬化中的作用及其调节机制。

方法

小鼠血管平滑肌细胞（vascular smooth muscle cells，VSMCs）分为对照（Con）组、吲哚酚硫酸盐（indophenol sulfate，IS）组、IS+Sp1组和IS+Sp1+sh-ABCA1组。Con组用0.1%二甲基亚砜（Dimethyl sulfoxide，DMSO）处理24 h，其他组加入250 nmol/L IS处理24 h。通过蛋白质印迹分析和DiI标记氧化型低密度脂蛋白（DiI-labeled oxidized low density lipoprotein，DiI-ox-LDL）染色分析Sp1/ABCA1蛋白表达和脂质积聚情况。80 只ApoE

-/-

小鼠随机分为4组，假手术（Sham）组、尿毒症加速动脉粥样硬化（uremia accelerated atherosclerosis，UAAS）组、UAAS+Vector组、UAAS+Sp1组，每组20只。通过主动脉油红O染色（OilRedO，ORO）检测主动脉脂质情况。

结果

IS浓度依赖性地促进细胞内DiI-ox-LDL荧光强度（

0.001）。与IS组相比，IS+Sp1组细胞内DiI-ox-LDL荧光强度明显降低（

0.001）。IS+Sp1+sh-ABCA1组细胞内DiI-ox-LDL荧光强度明显高于IS+Sp1组（

=0.015）。与Sham组相比，UAAS组、UAAS+Vector组主动脉和主动脉根、弓中ORO阳性面积明显增加（

0.001），和主动脉窦组织中α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）与Sp1的共定位水平明显减少（

=0.002、0.005）。UAAS+Sp1组主动脉、主动脉根和弓中ORO阳性面积较UAAS+Vector组明显减少（

0.001），和α-SMA与Sp1的共定位水平较UAAS+Vector组明显增加（

=0.008）。UAAS+Sp1组主动脉组织中Sp1和ABCA1蛋白表达水平明显高于UAAS+Vector组（

0.001）。

结论

尿毒症毒素IS可能通过抑制Sp1/ABCA1信号通路诱导VSMCs的脂质积聚，从而加速尿毒症内皮功能受损，促进动脉粥样硬化发展。

Abstract

Objective

To investigate the role of specificity protein 1（Sp1）/ATP-binding cassette transporter A1（ABCA1） signaling pathway in uremic atherosclerosis and its regulatory mechanism.

Methods

Mouse vascular smooth muscle cells（VSMCs） were divided into control（Con） group，indophenol sulfate（IS） group，IS+Sp1 group，and IS+Sp1+sh-ABCA1 group. The Con group was treated with 0.1% DMSO for 24 h，while other groups were treated with 250 nmol/L IS for 24 h. The protein expression of Sp1/ABCA1 and lipid accumulation were analyzed by Western blot and Dil-labeled oxidized low-density lipoprotein（Dil-ox-LDL） staining. Eighty ApoE

-/-

mice were randomly divided into four groups： sham group，uremia accelerated atherosclerosis（UAAS） group，UAAS+Vector group，and UAAS+Sp1 group，with 20 mice in each group. Aortic lipids were measured by oil red O（ORO） staining.

Results

IS promoted the fluorescence intensity of intracellular DiI-ox-LDL in a concentration-dependent manner（

0.05）. Compared with the IS group，the IS+Sp1 group had a significantly decreased fluorescence intensity of DiI-ox-LDL（

0.01）. The fluorescence intensity of DiI-ox-LDL in the IS+Sp1+sh-ABCA1 group was significantly higher than that in the IS+Sp1 group（

0.05）. Compared with the Sham group，the UAAS and UAAS+Vector groups had significantly increased ORO-positive areas in the aorta and aortic root and arch（

0.05） and significantly reduced colocation levels of alpha-smooth muscle actin （α-SMA） and Sp1 in the aortic sinus tissue（

0.05）. Compared with the UAAS+Vector group，the UAAS+Sp1 group had significantly reduced ORO-positive areas in the aorta and aortic root and arch（

0.05） and significantly increased colocation levels of α-SMA and Sp1（

0.05）. The protein expression levels of Sp1 and ABCA1 in the aortic tissue of the UAAS+Sp1 group were significantly higher than those of the UAAS+Vector group（

0.05）.

Conclusion

Uremic toxin IS may induce lipid accumulation in the VSMCs by inhibiting the Sp1/ABCA1 signaling pathway，thus accelerating endothelial dysfunction in uremia and promoting the progression of atherosclerosis.

关键词

Keywords

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