• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

肝组织中富含半胱氨酸的酸性分泌蛋白表达与非酒精性脂肪性肝病进展过程中的炎症小体激活相关，这种现象在肥胖症患者和实验鼠中均有体现。

Hepatic SPARC Expression Is Associated with Inflammasome Activation during the Progression of Non-Alcoholic Fatty Liver Disease in Both Mice and Morbidly Obese Patients.

机构信息

Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, CONICET-Universidad Austral, Av. Pte. Perón 1500, Pilar B1629AHJ, Argentina.

Pathological Anatomy Department, Hospital Universitario Austral, Universidad Austral, Av. Pte. Perón 1500, Pilar B1629AHJ, Argentina.

出版信息

Int J Mol Sci. 2023 Oct 2;24(19):14843. doi: 10.3390/ijms241914843.

DOI:10.3390/ijms241914843
PMID:37834291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10573696/
Abstract

The severity of non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to steatohepatitis, and it is not yet clearly understood which patients will progress to liver fibrosis or cirrhosis. SPARC (Secreted Protein Acidic and Rich in Cysteine) has been involved in NAFLD pathogenesis in mice and humans. The aim of this study was to investigate the role of SPARC in inflammasome activation, and to evaluate the relationship between the hepatic expression of inflammasome genes and the biochemical and histological characteristics of NAFLD in obese patients. In vitro studies were conducted in a macrophage cell line and primary hepatocyte cultures to assess the effect of SPARC on inflammasome. A NAFLD model was established in SPARC knockout (SPARC) and SPARC mice to explore inflammasome activation. A hepatic RNAseq database from NAFLD patients was analyzed to identify genes associated with SPARC expression. The results were validated in a prospective cohort of 59 morbidly obese patients with NAFLD undergoing bariatric surgery. Our results reveal that SPARC alone or in combination with saturated fatty acids promoted IL-1β expression in cell cultures. SPARC mice had reduced hepatic inflammasome activation during the progression of NAFLD. NAFLD patients showed increased expression of , , , and β. Gene ontology analysis revealed that genes positively correlated with SPARC are linked to inflammasome-related pathways during the progression of the disease, enabling the differentiation of patients between steatosis and steatohepatitis. In conclusion, SPARC may play a role in hepatic inflammasome activation in NAFLD.

摘要

非酒精性脂肪性肝病 (NAFLD) 的严重程度从单纯性脂肪变性到脂肪性肝炎不等，目前尚不清楚哪些患者会进展为肝纤维化或肝硬化。基质细胞衍生因子 1（SPARC）已参与到了小鼠和人类的 NAFLD 发病机制中。本研究旨在探讨 SPARC 在炎症小体激活中的作用，并评估肥胖患者 NAFLD 的炎症小体基因的肝表达与生化和组织学特征之间的关系。在巨噬细胞系和原代肝细胞培养物中进行了体外研究，以评估 SPARC 对炎症小体的影响。在 SPARC 敲除（SPARC）和 SPARC 小鼠中建立了 NAFLD 模型，以探讨炎症小体的激活。分析了 NAFLD 患者的肝 RNAseq 数据库，以鉴定与 SPARC 表达相关的基因。在接受减肥手术的 59 名肥胖合并 NAFLD 的前瞻性队列中验证了这些结果。我们的结果表明，SPARC 单独或与饱和脂肪酸一起在细胞培养物中促进了 IL-1β 的表达。SPARC 小鼠在 NAFLD 进展过程中肝炎症小体激活减少。NAFLD 患者表现出更高的表达。基因本体论分析显示，与 SPARC 呈正相关的基因与疾病进展过程中的炎症小体相关途径相关，能够区分患者的脂肪变性和脂肪性肝炎。总之，SPARC 可能在 NAFLD 的肝炎症小体激活中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/2f949432b1c3/ijms-24-14843-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/d4d93e91cbb7/ijms-24-14843-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/8480df160313/ijms-24-14843-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/7ee3b0c7672f/ijms-24-14843-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/cd4c81b2d087/ijms-24-14843-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/24d67a0e9845/ijms-24-14843-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/2f949432b1c3/ijms-24-14843-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/d4d93e91cbb7/ijms-24-14843-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/8480df160313/ijms-24-14843-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/7ee3b0c7672f/ijms-24-14843-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/cd4c81b2d087/ijms-24-14843-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/24d67a0e9845/ijms-24-14843-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/10573696/2f949432b1c3/ijms-24-14843-g006.jpg

相似文献

1
Hepatic SPARC Expression Is Associated with Inflammasome Activation during the Progression of Non-Alcoholic Fatty Liver Disease in Both Mice and Morbidly Obese Patients.肝组织中富含半胱氨酸的酸性分泌蛋白表达与非酒精性脂肪性肝病进展过程中的炎症小体激活相关，这种现象在肥胖症患者和实验鼠中均有体现。
Int J Mol Sci. 2023 Oct 2;24(19):14843. doi: 10.3390/ijms241914843.
2
SPARC inhibition accelerates NAFLD-associated hepatocellular carcinoma development by dysregulating hepatic lipid metabolism.抑制 SPARC 可通过扰乱肝脏脂质代谢加速非酒精性脂肪性肝病相关肝细胞癌的发展。
Liver Int. 2021 Jul;41(7):1677-1693. doi: 10.1111/liv.14857. Epub 2021 Mar 11.
3
NLRP3 inflammasome activation is required for fibrosis development in NAFLD.NLRP3炎性小体激活是NAFLD中纤维化发展所必需的。
J Mol Med (Berl). 2014 Oct;92(10):1069-82. doi: 10.1007/s00109-014-1170-1. Epub 2014 May 28.
4
Stellate cell expression of SPARC-related modular calcium-binding protein 2 is associated with human non-alcoholic fatty liver disease severity.富含半胱氨酸的酸性分泌蛋白相关模块化钙结合蛋白2在星状细胞中的表达与人类非酒精性脂肪性肝病的严重程度相关。
JHEP Rep. 2022 Oct 28;5(2):100615. doi: 10.1016/j.jhepr.2022.100615. eCollection 2023 Feb.
5
The role of SPARC (secreted protein acidic and rich in cysteine) in the pathogenesis of obesity, type 2 diabetes, and non-alcoholic fatty liver disease.富含半胱氨酸的酸性分泌蛋白（SPARC）在肥胖症、2 型糖尿病和非酒精性脂肪性肝病发病机制中的作用。
J Physiol Biochem. 2023 Nov;79(4):815-831. doi: 10.1007/s13105-022-00913-5. Epub 2022 Aug 26.
6
SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease.SPARC 表达与非酒精性脂肪性肝病啮齿动物和人类的肝损伤有关。
Sci Rep. 2018 Jan 15;8(1):725. doi: 10.1038/s41598-017-18981-9.
7
NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice.NLRP3炎性小体阻断可减轻小鼠实验性非酒精性脂肪性肝炎中的肝脏炎症和纤维化。
J Hepatol. 2017 May;66(5):1037-1046. doi: 10.1016/j.jhep.2017.01.022. Epub 2017 Feb 3.
8
Progression of non-alcoholic steatosis to steatohepatitis and fibrosis parallels cumulative accumulation of danger signals that promote inflammation and liver tumors in a high fat-cholesterol-sugar diet model in mice.在小鼠的高脂肪-高胆固醇-高糖饮食模型中，非酒精性脂肪变性进展为脂肪性肝炎和肝纤维化与促进炎症和肝肿瘤的危险信号的累积平行。
J Transl Med. 2015 Jun 16;13:193. doi: 10.1186/s12967-015-0552-7.
9
Inhibition of NLRP3 inflammasome by thioredoxin-interacting protein in mouse Kupffer cells as a regulatory mechanism for non-alcoholic fatty liver disease development.硫氧还蛋白相互作用蛋白对小鼠库普弗细胞中NLRP3炎性小体的抑制作用作为非酒精性脂肪性肝病发展的一种调节机制。
Oncotarget. 2017 Jun 6;8(23):37657-37672. doi: 10.18632/oncotarget.17489.
10
Cathepsin B inhibition ameliorates the non-alcoholic steatohepatitis through suppressing caspase-1 activation.组织蛋白酶 B 抑制通过抑制半胱氨酸天冬氨酸蛋白酶-1 的激活改善非酒精性脂肪性肝炎。
J Physiol Biochem. 2018 Nov;74(4):503-510. doi: 10.1007/s13105-018-0644-y. Epub 2018 Jul 17.

引用本文的文献

1
Gut microbiota and protein-to-protein ratios in NAFLD: insights from Mendelian randomization and murine studies.非酒精性脂肪性肝病中的肠道微生物群与蛋白质比例：孟德尔随机化和小鼠研究的见解
Front Nutr. 2025 Jul 18;12:1597390. doi: 10.3389/fnut.2025.1597390. eCollection 2025.

本文引用的文献

1
Key genes associated with non-alcoholic fatty liver disease and hepatocellular carcinoma with metabolic risk factors.与非酒精性脂肪性肝病和伴有代谢危险因素的肝细胞癌相关的关键基因。
Front Genet. 2023 Mar 6;14:1066410. doi: 10.3389/fgene.2023.1066410. eCollection 2023.
2
Stellate cell expression of SPARC-related modular calcium-binding protein 2 is associated with human non-alcoholic fatty liver disease severity.富含半胱氨酸的酸性分泌蛋白相关模块化钙结合蛋白2在星状细胞中的表达与人类非酒精性脂肪性肝病的严重程度相关。
JHEP Rep. 2022 Oct 28;5(2):100615. doi: 10.1016/j.jhepr.2022.100615. eCollection 2023 Feb.
3
Characterization of signature trends across the spectrum of non-alcoholic fatty liver disease using deep learning method.
使用深度学习方法对非酒精性脂肪性肝病全谱特征趋势进行表征
Life Sci. 2023 Feb 1;314:121195. doi: 10.1016/j.lfs.2022.121195. Epub 2022 Nov 24.
4
The role of SPARC (secreted protein acidic and rich in cysteine) in the pathogenesis of obesity, type 2 diabetes, and non-alcoholic fatty liver disease.富含半胱氨酸的酸性分泌蛋白（SPARC）在肥胖症、2 型糖尿病和非酒精性脂肪性肝病发病机制中的作用。
J Physiol Biochem. 2023 Nov;79(4):815-831. doi: 10.1007/s13105-022-00913-5. Epub 2022 Aug 26.
5
The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging.基质细胞蛋白 SPARC 在衰老过程中诱导巨噬细胞产生炎症性干扰素反应。
Immunity. 2022 Sep 13;55(9):1609-1626.e7. doi: 10.1016/j.immuni.2022.07.007. Epub 2022 Aug 12.
6
Plasma Aldo-Keto Reductase Family 1 Member B10 as a Biomarker Performs Well in the Diagnosis of Nonalcoholic Steatohepatitis and Fibrosis.血浆醛酮还原酶家族 1 成员 B10 作为生物标志物在非酒精性脂肪性肝炎和纤维化的诊断中表现良好。
Int J Mol Sci. 2022 May 1;23(9):5035. doi: 10.3390/ijms23095035.
7
Role of the Inflammasome in Liver Disease.炎症小体在肝脏疾病中的作用。
Annu Rev Pathol. 2022 Jan 24;17:345-365. doi: 10.1146/annurev-pathmechdis-032521-102529. Epub 2021 Nov 9.
8
Transaminase Concentrations Cannot Separate Non-Alcoholic Fatty Liver and Non-Alcoholic Steatohepatitis in Morbidly Obese Patients Irrespective of Histological Algorithm.转氨基酶浓度不能区分病态肥胖患者的非酒精性脂肪肝和非酒精性脂肪性肝炎，无论采用何种组织学算法。
Dig Dis. 2022;40(5):644-653. doi: 10.1159/000519317. Epub 2021 Sep 1.
9
Mechanisms and disease consequences of nonalcoholic fatty liver disease.非酒精性脂肪性肝病的机制及疾病后果
Cell. 2021 May 13;184(10):2537-2564. doi: 10.1016/j.cell.2021.04.015.
10
Diagnostic management of nonalcoholic fatty liver disease: a transformational period in the development of diagnostic and predictive tools-a narrative review.非酒精性脂肪性肝病的诊断管理：诊断和预测工具发展中的转型期——一篇叙述性综述
Ann Transl Med. 2021 Apr;9(8):727. doi: 10.21037/atm-20-4723.