CD36作为针对非酒精性脂肪性肝病（NAFLD）细胞筛选出的功能性DNA适配体NAFLD01的分子靶点。
CD36 as a Molecular Target of Functional DNA Aptamer NAFLD01 Selected against NAFLD Cells.
作者信息
Pu Ying, Xiang Juan, Zhang Xinxu, Deng Yuanyuan, Liu Huixia, Tan Weihong
机构信息
Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.
出版信息
Anal Chem. 2021 Mar 2;93(8):3951-3958. doi: 10.1021/acs.analchem.0c04866. Epub 2021 Feb 17.
The aim of this study was to identify the target of nonalcoholic fatty liver disease (NAFLD) cell-specific aptamer NAFLD01 and investigate its effect on lipid metabolism . A distinct membrane protein of NAFLD cells pulled down by NAFLD01 was analyzed by mass spectrometry to determine target candidates, and affinity of NAFLD01 to target-protein-silent NAFLD cells was detected to validate it. Knockdown of CD36 abolished the binding of NAFLD01, and its binding affinity was associated with membrane-bound CD36. NAFLD01 affinity for NAFLD cells was proportional to the CD36 expression level. Moreover, compared to random sequences, NAFLD01 showed better recognition for both mouse and human tissue sections of NAFLD. Importantly, NAFLD01 could ameliorate liver fat deposition through interaction with CD36 . Therefore, aptamer NAFLD01 could act as an effective and safe targeted drug for NAFLD. NAFLD01 is the first reported CD36-specific aptamer. This aptamer can improve hepatocyte steatosis specifically binding to CD36. This study provides a molecular tool to investigate the mechanism of CD36 in NAFLD.
本研究旨在鉴定非酒精性脂肪性肝病（NAFLD）细胞特异性适配体NAFLD01的靶点，并研究其对脂质代谢的影响。通过质谱分析由NAFLD01拉下的NAFLD细胞的一种独特膜蛋白，以确定候选靶点，并检测NAFLD01对靶蛋白沉默的NAFLD细胞的亲和力以进行验证。敲低CD36消除了NAFLD01的结合，其结合亲和力与膜结合的CD36相关。NAFLD01对NAFLD细胞的亲和力与CD36表达水平成正比。此外，与随机序列相比，NAFLD01对NAFLD的小鼠和人类组织切片表现出更好的识别能力。重要的是，NAFLD01可通过与CD36相互作用改善肝脏脂肪沉积。因此，适配体NAFLD01可作为一种有效且安全的NAFLD靶向药物。NAFLD01是首个报道的CD36特异性适配体。该适配体可通过特异性结合CD36改善肝细胞脂肪变性。本研究提供了一种研究CD36在NAFLD中作用机制的分子工具。
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