吉林大学学报（医学版）2026，Vol.52Issue(2)：299-307,9.DOI:10.13481/j.1671-587X.20260201
特异性蛋白1调控脂肪细胞中弗林蛋白酶表达对白脂素分泌的影响及其机制
Effect of Furin expression regulated by specific protein 1 on asprosin secretion in adipocytes and its mechanism
摘要
Abstract
Objective:To investigate the transcriptional regulation mechanism of the Furin gene in adipose tissue under obesity conditions and its effect on the secretion of the adipokine asprosin.Methods:Twenty-four C57BL/6J mice were randomly divided into normal control diet(NCD)group and high-fat diet(HFD)group,with 12 mice in each group.The mice were fed for 12 consecutive weeks to establish the diet-induced obesity models.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Furin,fibrillin 1(FBN1),and the candidate transcription factor specificity protein 1(SP1)mRNA in subcutaneous white adipose tissue(WAT)(sWAT)and epididymal WAT(eWAT)of the mice in two groups.Candidate transcription factors for the Furin gene promoter region were screened based on the JASPAR database.In the 293T cells,the SP1 over-expression plasmid(pcDNA-SP1 group)and its control plasmid containing green fluorescence protein(GFP)(pcDNA-GFP group)were transfected.Simultaneously,a dual-luciferase reporter vector containing the Furin promoter region was co-transfected with the aforementioned plasmids to verify the regulatory interaction between SP1 and the Furin promoter.The stromal vascular fraction(SVF)cells from sWAT were isolated and induced to differentiate into mature adipocytes.SP1(Ad-SP1 group)or GFP control(Ad-GFP group)was overexpressed via adenoviral transduction.Western blotting method and enzyme-linked immunosorbent assay(ELISA)were used to detect the expression levels of SP1 and Furin proteins in cells in various groups and the levels of asprosin in the cell supernatant in Ad-GFP and Ad-SP1 groups,respectively.Results:Compared with NCD group,the body weight,sWAT weight,and eWAT weight of the mice in HFD group were significantly increased(P<0.001).Compared with NCD group,the expression levels of Furin and SP1 mRNA in sWAT and eWAT of the mice in HFD group were significantly increased(P<0.001).JASPAR database prediction suggested that SP1 was a core candidate factor regulating Furin transcription.In the dual-luciferase experiment,compared with pcDNA-GFP group,the luciferase activity in 293T cells in pcDNA-SP1 group was significantly increased(P<0.001).Compared with Ad-GFP group,the expression levels of SP1 and Furin proteins in SVF-derived mature adipocytes in Ad-SP1 group were significantly increased(P<0.001),and the level of asprosin in the cell supernatant was significantly increased(P<0.001).Conclusion:The expression of SP1 mRNA in WAT and adipocytes of obese mice was up-regulated.SP1 can enhance the transcriptional activity of Furin by directly binding to its promoter region.SP1 overexpression may upregulate the expression level of Furin protein in adipocytes,promoting the secretion of asprosin.关键词
肥胖/弗林蛋白酶/特异性蛋白1/白脂素/转录调控Key words
Obesity/Furin/Specificity protein 1/Asprosin/Transcriptional regulation分类
医药卫生引用本文复制引用
董振亚,张鑫铬,邓娅娅,朱井玲,菅辉玲,张云华..特异性蛋白1调控脂肪细胞中弗林蛋白酶表达对白脂素分泌的影响及其机制[J].吉林大学学报（医学版）,2026,52(2):299-307,9.基金项目
国家自然科学基金项目(82260126,32460221) （82260126,32460221）
新疆生产建设兵团科技局指导性科技计划项目(2024ZD020) （2024ZD020）
新疆维吾尔自治区克拉玛依市中心医院院内项目(20240101) （20240101）
