Extracellular vesicles derived from liver sinusoidal endothelial cells inhibit the activation of hepatic stellate cells and Kupffer cells in vitro

被引：9
作者：
Wang, Junyu [1 ]
Wu, Zongmei [1 ]
Xia, Mengmeng [1 ]
Salas, Sandra Serna [1 ]
Ospina, Johanna Arroyave [1 ]
Buist-Homan, Manon [1 ,3 ]
Harmsen, Martin C. [1 ,2 ]
Moshage, Han [1 ,3 ]
机构：
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Groningen, Netherlands
[3] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, Groningen, Netherlands
来源：
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2024年 / 1870卷 / 03期
关键词：
Liver sinusoidal endothelial cells; Extracellular vesicles; Metabolic dysfunction -associated steatotic liver; disease; Hepatic stellate cells; Kupffer cells; Fibrosis; NONALCOHOLIC STEATOHEPATITIS; FIBROSIS; INFLAMMATION; PROGRESSION; DISEASE; MICE;
D O I：
10.1016/j.bbadis.2024.167020
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Liver sinusoidal endothelial cells (LSECs) play a crucial role in maintaining liver microcirculation and exchange of nutrients in the liver and are thought to be involved in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). The activation of hepatic stellate cells (HSCs) and Kupffer cells (KCs) has been considered to be responsible for the onset of liver fibrosis and the aggravation of liver injury. However, the paracrine regulatory effects of LSECs in the development of MASLD, in particular the role of LSEC-derived extracellular vesicles (EVs) remains unclear. Therefore, the aim of the present study was to investigate the influence of LSEC-derived EVs on HSCs and KCs. Primary rat LSECs, HSCs and KCs were isolated from male Wistar rats. LSEC-derived EVs were isolated from conditioned medium by ultracentrifugation and analyzed by nanoparticle tracking analysis, and expression of specific markers. LSEC-derived EVs reduced the expression of activation markers in activated HSCs but did not affect quiescent HSCs. Also, LSEC-derived EVs suppressed proliferation of activated HSCs activation, as assessed by Xcelligence and BrdU assay. LSEC-derived EVs also increased the expression of inflammatory genes in HSCs that normally are lowly expression during their activation. In contrast, EVs decreased the expression of inflammatory genes in activated KCs. In summary, our results suggest that LSEC-derived EVs may attenuate the fibrogenic phenotype of activated HSCs and the inflammatory phenotype of KCs. Our results show promise for LSEC-derived EVs as therapeutic moieties to treat MASLD. In addition, these EVs might prove of diagnostic value.
引用
收藏
页数：12
相关论文
共 39 条
[1]  
Avadanei R, 2013, ROM J MORPHOL EMBRYO, V54, P479
[2]   NAFLD: A multisystem disease [J].
Byrne, Christopher D. ;
Targher, Giovanni .
JOURNAL OF HEPATOLOGY, 2015, 62 :S47-S64
[3]   NLRP3 Deletion Inhibits the Non-alcoholic Steatohepatitis Development and Inflammation in Kupffer Cells Induced by Palmitic Acid [J].
Cai, Can ;
Zhu, Xiwen ;
Li, Peizhi ;
Li, Jinzheng ;
Gong, Jianping ;
Shen, Wei ;
He, Kun .
INFLAMMATION, 2017, 40 (06) :1875-1883
[4]   ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials [J].
Calle, Roberto A. ;
Amin, Neeta B. ;
Carvajal-Gonzalez, Santos ;
Ross, Trenton T. ;
Bergman, Arthur ;
Aggarwal, Sudeepta ;
Crowley, Collin ;
Rinaldi, Anthony ;
Mancuso, Jessica ;
Aggarwal, Naresh ;
Somayaji, Veena ;
Inglot, Malgorzata ;
Tuthill, Theresa A. ;
Kou, Kou ;
Boucher, Magalie ;
Tesz, Greg ;
Dullea, Robert ;
Bence, Kendra K. ;
Kim, Albert M. ;
Pfefferkorn, Jeffrey A. ;
Esler, William P. .
NATURE MEDICINE, 2021, 27 (10) :1836-+
[5]  
Cheng BQ, 2021, J BUON, V26, P435
[6]   FABP4 and MMP9 levels identified as predictive factors for poor prognosis in patients with nonalcoholic fatty liver using data mining approaches and gene expression analysis [J].
Coilly, Audrey ;
Desterke, Christophe ;
Guettier, Catherine ;
Samuel, Didier ;
Chiappini, Franck .
SCIENTIFIC REPORTS, 2019, 9 (1)
[7]   Liver Sinusoidal Endothelial Cells in Hepatic Fibrosis [J].
DeLeve, Laurie D. .
HEPATOLOGY, 2015, 61 (05) :1740-1746
[8]   Defining paediatric metabolic (dysfunction)-associated fatty liver disease: an international expert consensus statement [J].
Eslam, Mohammed ;
Alkhouri, Naim ;
Vajro, Pietro ;
Baumann, Ulrich ;
Weiss, Ram ;
Socha, Piotr ;
Marcus, Claude ;
Lee, Way Seah ;
Kelly, Deirdre ;
Porta, Gilda ;
El-Guindi, Mohamed A. ;
Alisi, Anna ;
Mann, Jake P. ;
Mouane, Nezha ;
Baur, Louise A. ;
Dhawan, Anil ;
George, Jacob .
LANCET GASTROENTEROLOGY & HEPATOLOGY, 2021, 6 (10) :864-873
[9]   Redefining non-alcoholic fatty liver disease: what's in a name? [J].
不详 .
LANCET GASTROENTEROLOGY & HEPATOLOGY, 2020, 5 (05) :419-419
[10]   Kupffer-derived matrix metalloproteinase-9 contributes to liver fibrosis resolution [J].
Feng, Min ;
Ding, Jie ;
Wang, Min ;
Zhang, Jie ;
Zhu, Xinhua ;
Guan, Wenxian .
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2018, 14 (09) :1033-1040
1234