山东医药2026，Vol.66Issue(5)：44-49,6.DOI:10.3969/j.issn.1002-266X.2026.05.009
CALR、PLA2G4A在代谢相关脂肪性肝病脂质代谢中的作用及调控关系
Roles and regulatory relationships of CALR and PLA2G4A in lipid metabolism in metabolic-associated fatty liver disease
摘要
Abstract
Objective To investigate the roles of calreticulin(CALR)and phospholipase A2 group IVA(PLA2G4A)in lipid metabolism in metabolic-associated fatty liver disease(MAFLD),and to conduct a preliminary analy-sis of the regulatory relationship between CALR and PLA2G4A.Methods A model of hepatic steatosis in HepG2 cells was established using a combination of free fatty acids and insulin.HepG2 cells experiment was divided into two experi-ments:CALR-knockdown and PLA2G4A-knockdown experiments.In the CALR-knockdown experiment,we subdivided the cells into the control group,model group,model+CALR-knockdown negative control(NC)group,and model+CALR-knockdown group;in the PLA2G4A knockdown experiment,we divided the cells into the control group,model group,model+PLA2G4A knockdown negative control(NC)group,and model+PLA2G4A knockdown group,respective-ly.Oil Red O staining was used to visualize cellular lipid accumulation,and a triglyceride(TG)assay kit was used to mea-sure cellular TG levels;RT-qPCR and Western blotting were employed to detect the mRNA and protein expression of CALR,PLA2G4A,sterol regulatory element-binding protein(SREBP),and fatty acid synthase(FAS).Actinomycin D(ActD)was used to inhibit cellular transcription.Cells were harvested at 1,8,and 16 h after ActD treatment in the model group and the model+CALR knockdown group,and changes in PLA2G4A mRNA and protein expression were detected.RIP-PCR was used to detect the interaction between CALR and PLA2G4A mRNA,and the input percentage and enrich-ment fold were calculated.Results Eosin-O staining results showed that,compared with the control group,the model group exhibited a significant increase in red lipid droplets within cells;compared with the model group,both the CALR knockdown group and the PLA2G4A knockdown group showed a reduction in red lipid droplets within cells.In the CALR knockdown section,cellular lipid accumulation and TG levels were as follows:model group,model+CALR knockdown NC group>model+CALR knockdown group>control group(all P<0.01).In the PLA2G4A knockdown section,cellular lipid accumulation and TG levels were higher in the model group and the model+PLA2G4A knockdown NC group than in the model+PLA2G4A knockdown group,which in turn was higher than those of the control group(all P<0.01).In the CALR knockdown group,the mRNA expression of CALR,PLA2G4A,SREBP,and FAS was higher in the model group and the model+CALR knockdown NC group than in the model+CALR knockdown group and the control group;the pro-tein expression of SREBP and FAS in the model group and the model+CALR knockdown NC group was higher than that in the model+CALR knockdown group and the control group;CALR protein expression was as follows:model group,model+CALR knockdown NC group>model+CALR knockdown group,control group;PLA2G4A protein expression was as fol-lows:model group,model+CALR knockdown NC group,model+CALR knockdown group>control group(all P<0.05).In the PLA2G4A knockdown section,the expression of CALR,PLA2G4A,SREBP,and FAS mRNA and proteins were as follows:the model group and the model+PLA2G4A knockdown NC group>the model+PLA2G4A knockdown group>the control group(all P<0.05).In both the model group and the model+CALR knockdown group,PLA2G4A mRNA and protein expression decreased with prolonged ActD treatment,and at each time point,PLA2G4A mRNA and protein expression in the model+CALR knockdown group were lower than those in the model group at the same time points(all P<0.05).In the model+CALR knockdown group,both the percentage of PLA2G4A mRNA input and the enrichment fold were lower than those in the model group(all P<0.05).Conclusions CALR and PLA2G4A jointly participate in the process of lipid metabolism abnormalities in MAFLD.Knocking down either CALR or PLA2G4A reduces lipid accumu-lation in the HepG2 fatty degeneration model,accompanied by decreased expression of lipid metabolism-related molecules such as SREBP and FAS;down-regulation of CALR leads to reduced PLA2G4A expression,suggesting that CALR may be involved in the regulation of PLA2G4A at the post-transcriptional level.关键词
代谢相关脂肪性肝病/钙网蛋白/磷脂酶A2组IVA/脂质代谢Key words
metabolic-associated fatty liver disease/calreticulin/phospholipase A2 group IVA/lipid metabolism分类
医药卫生引用本文复制引用
张伟彬,冯亚宁,苏蕊,纪文静..CALR、PLA2G4A在代谢相关脂肪性肝病脂质代谢中的作用及调控关系[J].山东医药,2026,66(5):44-49,6.基金项目
省部共建中亚高发病成因与防治国家重点实验室-新医大二附院联合基金项目(SKL-HIDCA-2023-EF1). （SKL-HIDCA-2023-EF1）
