Histidine-rich glycoprotein in metabolic dysfunction-associated steatohepatitis-related disease progression and liver carcinogenesis

脂肪性肝炎 肝硬化 肝细胞癌 纤维化 医学 脂肪肝 血管生成 慢性肝病 肝病 内科学 病理 癌症研究 胃肠病学 疾病
作者
Beatrice Foglia,Salvatore Sutti,Stefania Cannito,Chiara Rosso,Marina Maggiora,Alice Casalino,Claudia Bocca,Erica Novo,Francesca Protopapa,Naresh Naik Ramavath,Alessia Provera,Alessandro Gambella,Elisabetta Bugianesi,Frank Tacke,Emanuele Albano,Maurizio Parola
出处
期刊:Frontiers in Immunology [Frontiers Media SA]
卷期号:15 被引量:2
标识
DOI:10.3389/fimmu.2024.1342404
摘要

Background Metabolic dysfunction-associated steatotic liver disease (MASLD), previously non-alcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease worldwide. In 20%–30% of MASLD patients, the disease progresses to metabolic dysfunction-associated steatohepatitis (MASH, previously NASH) which can lead to fibrosis/cirrhosis, liver failure as well as hepatocellular carcinoma (HCC). Here we investigated the role of histidine-rich glycoprotein (HRG), a plasma protein produced by hepatocytes, in MASLD/MASH progression and HCC development. Methods The role of HRG was investigated by morphological, cellular, and molecular biology approaches in (a) HRG knock-out mice (HRG −/− mice) fed on a CDAA dietary protocol or a MASH related diethyl-nitrosamine/CDAA protocol of hepatocarcinogenesis, (b) THP1 monocytic cells treated with purified HRG, and (c) well-characterized cohorts of MASLD patients with or without HCC. Results In non-neoplastic settings, murine and clinical data indicate that HRG increases significantly in parallel with disease progression. In particular, in MASLD/MASH patients, higher levels of HRG plasma levels were detected in subjects with extensive fibrosis/cirrhosis. When submitted to the pro-carcinogenic protocol, HRG −/− mice showed a significant decrease in the volume and number of HCC nodules in relation to decreased infiltration of macrophages producing pro-inflammatory mediators, including IL-1β, IL-6, IL-12, IL-10, and VEGF as well as impaired angiogenesis. The histopathological analysis (H-score) of MASH-related HCC indicate that the higher HRG positivity in peritumoral tissue significantly correlates with a lower overall patient survival and an increased recurrence. Moreover, a significant increase in HRG plasma levels was detected in cirrhotic (F4) patients and in patients carrying HCC vs. F0/F1 patients. Conclusion Murine and clinical data indicate that HRG plays a significant role in MASLD/MASH progression to HCC by supporting a specific population of tumor-associated macrophages with pro-inflammatory response and pro-angiogenetic capabilities which critically support cancer cell survival. Furthermore, our data suggest HRG as a possible prognostic predictor in HCC patients with MASLD/MASH-related HCCs.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
wan完成签到,获得积分10
刚刚
Pyrene发布了新的文献求助10
1秒前
ZWZ完成签到,获得积分10
1秒前
文文完成签到,获得积分10
1秒前
逗逗完成签到,获得积分10
1秒前
小二郎应助mmx采纳,获得10
1秒前
Neutrino完成签到,获得积分10
1秒前
大脚发布了新的文献求助100
2秒前
2秒前
2秒前
兴钬完成签到,获得积分10
2秒前
ShenghuiH发布了新的文献求助10
2秒前
Tian发布了新的文献求助10
3秒前
木木酱完成签到,获得积分10
3秒前
邓谷云完成签到,获得积分10
3秒前
niumm发布了新的文献求助10
5秒前
激动的新筠完成签到,获得积分10
5秒前
裘问薇完成签到,获得积分10
5秒前
CipherSage应助orchid采纳,获得10
5秒前
sophia完成签到 ,获得积分10
5秒前
Jayce完成签到,获得积分10
6秒前
6秒前
6秒前
福建农林太学完成签到,获得积分10
6秒前
鱿鱼炒黄瓜完成签到,获得积分10
7秒前
ffhjlfwex发布了新的文献求助10
7秒前
小麦完成签到,获得积分10
8秒前
8秒前
淡然的奎完成签到,获得积分10
8秒前
wuyy完成签到,获得积分10
9秒前
10秒前
10秒前
10秒前
Bsisoy完成签到,获得积分10
10秒前
11秒前
last炫神应助陳.采纳,获得10
11秒前
重要紫丝完成签到,获得积分10
11秒前
min17完成签到 ,获得积分10
12秒前
12秒前
xj发布了新的文献求助10
12秒前
高分求助中
Evolution 2024
Experimental investigation of the mechanics of explosive welding by means of a liquid analogue 1060
Die Elektra-Partitur von Richard Strauss : ein Lehrbuch für die Technik der dramatischen Komposition 1000
How to Create Beauty: De Lairesse on the Theory and Practice of Making Art 1000
Gerard de Lairesse : an artist between stage and studio 670
大平正芳: 「戦後保守」とは何か 550
LNG地下タンク躯体の構造性能照査指針 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3004872
求助须知:如何正确求助?哪些是违规求助? 2664288
关于积分的说明 7221177
捐赠科研通 2300923
什么是DOI,文献DOI怎么找? 1220238
科研通“疑难数据库(出版商)”最低求助积分说明 594615
版权声明 593226