基于生信分析探索PNPLA3表达对代谢相关脂肪性肝病的影响

肝脏 ›› 2025, Vol. 30 ›› Issue (9): 1195-1199.

基于生信分析探索PNPLA3表达对代谢相关脂肪性肝病的影响

何晓萱, 马雪儿, 杨雪霞, 李琴, 朱凯, 蔡雯

830000 乌鲁木齐新疆医科大学护理学院(何晓萱,李琴,蔡雯);201204 上海同济大学附属妇产科医院(马雪儿);830001 乌鲁木齐新疆维吾尔自治区中医药学会(杨雪霞);236008 阜阳阜阳幼儿师范高等专科学校护理学院(朱凯)

收稿日期:2024-07-31 出版日期:2025-09-30 发布日期:2025-11-05
通讯作者: 蔡雯,Email:caiwen820602@163.com
基金资助:
新疆维吾尔族自治区省部共建中亚高发病成因与防治国家重点实验室基金代谢病专项(SKL-HIDCA-2022-DX5 );新疆维吾尔族自治区自然科学基金面上项目(2020D01C70)

Exploring the impact of PNPLA3 expression on metabolic related fatty liver disease based on bioinformatics analysis

HE Xiao-xuan¹, MA Xue-er², YANG Xue-xia³, LI Qin¹, ZHU Kai⁴, CAI Wen¹

1. School of Nursing, Xinjiang Medical University, Urumqi 830000, China;
2. Obstetrics and Gynecology Hospital Affiliated to Tongji University, Shanghai 201204, China;
3. Xinjiang Uygur Autonomous Region Association of Traditional Chinese Medicine, Urumqi 830001, China;
4. School of Nursing, Fuyang College of Preschool Education, Fuang 236008, China

Received:2024-07-31 Online:2025-09-30 Published:2025-11-05
Contact: CAI Wen, Email: caiwen820602@163.com

摘要/Abstract

摘要： 目的通过生物信息学分析探索patatin样磷脂酶域蛋白3(PNPLA3)在代谢相关脂肪性肝病(MAFLD)中的表达和功能富集。方法建立慢病毒转染PNPLA3不同表达MAFLD细胞模型, 筛选PNPLA3差异基因,富集分析确定基因生物学意义,表达差异分析确定PNPLA3不同表达涉及通路及其与代谢相关脂肪性肝病的关系。结果基因组进行序列比对,比对率从97.27%到97.96%不等;共检测到表达基因32 788个;表达转录本共158 930个。与模型组相比,PNPLA过表达组差异表达基因有2 748个,其中上调表达基因1 264个,下调表达基因1 484个。PNPLA3过表达组在生物学过程中主要有细胞过程、生物调节、代谢过程、细胞成分组织或生物发生、对刺激的反应等。在分子功能中主要有结合、催化活性、转录调节活性和分子功能调节剂等。KEGG通路富集分析显示,PNPLA3过表达组的通路有干细胞多能性调控信号通路、ECM受体相互作用、IL-17信号通路、化学致癌－活性氧、人乳头状瘤病毒感染、脂质与动脉粥样硬化。结论 PNPLA3在MAFLD中表达升高,参与包括生物调节、代谢过程等反应。

Abstract: Objective To Explore the expression and functional enrichment of PNPLA3 in metabolic related fatty liver disease (MAFLD) through bioinformatics analysis. Methods A slow virus transfection model for PNPLA3 over-expression in MAFLD cells was established. The differentially expressed genes were screened from PNPLA3 over-expressed cells. Enrichment analysis was performed to determine the biological significance of these genes. Differential expression analysis was performed to determine the pathways involved in different expression levels of PNPLA3 and its relationship with MAFLD. Results The alignment rates of genomic sequence alignment ranging from 97.27% to 97.96%; A total of 32 788 expressed genes were detected through analysis; A total of 158 930 transcripts were expressed; Compared with the model control group, the PNPLA3 overexpression group had 2 748 differentially expressed genes, including 1 264 upregulated genes and 1 484 downregulated genes. The differentially expressed genes in The PNPLA3 overexpression group mainly includes genes that were involved in cellular processes, biological regulation, metabolic processes, cellular component organization or biogenesis, and response to stimuli in biological processes. In molecular functions, there were mainly binding, catalytic activity, transcriptional regulatory activity, and molecular function regulators. The enrichment analysis of KEGG pathway showed that the pathways of PNPLA3 overexpression group included stem cell pluripotency regulation signaling pathway, ECM receptor interaction, IL-17 signaling pathway, chemical carcinogenesis, reactive oxygen species, human papillomavirus infection, lipid and atherosclerosis. Conclusion The expression level PNPLA3 is upregulated, and associated with the occurrence and development of MAFLD. This protein participates in reactions including biological regulation and metabolic processes.

Key words: Bioinformatics, MAFLD, PNPLA3, Gene expression, GO/KEGG analysis, Biomarker

何晓萱, 马雪儿, 杨雪霞, 李琴, 朱凯, 蔡雯. 基于生信分析探索PNPLA3表达对代谢相关脂肪性肝病的影响[J]. 肝脏, 2025, 30(9): 1195-1199.

HE Xiao-xuan, MA Xue-er, YANG Xue-xia, LI Qin, ZHU Kai, CAI Wen. Exploring the impact of PNPLA3 expression on metabolic related fatty liver disease based on bioinformatics analysis[J]. Chinese Hepatolgy, 2025, 30(9): 1195-1199.

/ 推荐

参考文献

[1] 胡丽平,蔡华,李情娇,等.代谢相关脂肪性肝病发病机制的研究[J].医学信息, 2023, 36(23): 174-179.
[2] Lindén D, Romeo S. Therapeutic opportunities for the treatment of NASH with genetically validated targets[J]. J Hepatol, 2023, 79(4): 1056-1064.
[3] Wijarnpreecha K, Scribani M, Raymond P, et al. PNPLA3 gene polymorphism and liver and extrahepatic cancer-related mortality in the United States[J]. Clin Gastroenterol Hepatol, 2021, 19(5):1064-1066.
[4] Cherubini A, Casirati E, Tomasi M, et al. PNPLA3 as a therapeutic target for fatty liver disease: the evidence to date[J]. Expert Opin Ther Targets, 2021, 25(12):1033-1043.
[5] Borén J, Adiels M, Björnson E,et al.Effects of PNPLA3 I148M on hepatic lipid and very-low-density lipoprotein metabolism in humans [J]. J Intern Med, 2022, 291(2):218-223.
[6] Johnson S, Bao H, McMahon C, et al.Substrate-specific function of PNPLA3 facilitates hepatic VLDL-triglyceride secretion during stimulated lipogenesis[J].Preprint, bioRxiv, 2023, 2023.08.30, 553213.
[7] Youssef S S, Abbas EAER, Youness R A, et al. PNPLA3 and IL 28B signature for predicting susceptibility to chronic hepatitis C infection and fibrosis progression [J]. Arch Physiol Biochem, 2022, 128(2):483-489.
[8] Chen V L, Oliveri A, Miller M J, et al.PNPLA3 genotype and diabetes identify patients with nonalcoholic fatty liver disease at high risk of incident cirrhosis [J]. Gastroenterology, 2023, 164(6):966-977.e17.
[9] Tacke F, Puengel T, Loomba R, et al. An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH [J]. J Hepatol, 2023, 79(2):552-566.
[10] Yuan L, Terrrault N A. PNPLA3 and nonalcoholic fatty liver disease: towards personalized medicine for fatty liver[J]. Hepatobiliary Surg Nutr, 2020, 9(3):353-356.
[11] Tilson S G, Morell C M, Lenaerts A S, et al. Modeling pnpla3-associated nafld using human-induced pluripotent stem cells[J]. Hepatology, 2021, 74(6): 2998-3017.
[12] Yuan S, Liu H, Yuan D, et al. PNPLA3 I148M mediates the regulatory effect of NF-kB on inflammation in PA-treated HepG2 cells[J]. J Cell Mol Med, 2020, 24(2):1541-1552.
[13] Witzel H R, Schwittai I M G, Hartmann N, et al. PNPLA3(I148M) inhibits lipolysis by perilipin-5-dependent competition with ATGL[J]. Cells, 2022, 12(1):73.
[14] Park J, Zhao Y, Zhang F, et al. IL-6/STAT3 axis dictates the PNPLA3-mediated susceptibility to non-alcoholic fatty liver disease[J]. J Hepatol, 2023, 78(1):45-56.
[15] Lonardo A, Arab J P, Arrese M. Perspectives on precision medicine approaches to nafld diagnosis and management[J]. Adv Ther, 2021, 38(5): 2130-2158.
[16] Fang X , Miao R , Wei J ,et al.Advances in multi-omics study of biomarkers of glycolipid metabolism disorder[J].Comput Struct Biotechnol J, 2022, 20:5935-5951.