Ectodysplasin-A mRNA in exosomes released from activated hepatic stellate cells stimulates macrophage response.
Animals
Ectodysplasins
/ metabolism
Edar Receptor
Exosomes
/ metabolism
Hepatic Stellate Cells
/ metabolism
Humans
Interleukin-6
/ metabolism
Liver Cirrhosis
/ pathology
Liver Neoplasms
/ pathology
Macrophages
/ metabolism
RNA, Messenger
/ genetics
RNA, Small Interfering
/ metabolism
Rats
Tumor Necrosis Factor-alpha
/ metabolism
Ectodysplasin-A
Exosome
Hepatic stellate cell
Interleukin-6
Macrophage
Tumor necrosis factor-α
Journal
Experimental cell research
ISSN: 1090-2422
Titre abrégé: Exp Cell Res
Pays: United States
ID NLM: 0373226
Informations de publication
Date de publication:
15 10 2022
15 10 2022
Historique:
received:
18
02
2022
revised:
21
06
2022
accepted:
20
07
2022
pubmed:
15
8
2022
medline:
14
9
2022
entrez:
14
8
2022
Statut:
ppublish
Résumé
The interaction between activated hepatic stellate cells (aHSCs) and macrophages is central to liver fibrosis development. The cargo contained within aHSC exosomes (aHSC-EXOs) and how aHSC-EXOs affect macrophage function is poorly understood. RNA from aHSC-EXOs was separated into small (<200-basepairs) and large (≥200-basepairs) RNA species, transfected into macrophages, and macrophage IL-6 and TNFα mRNA expression and protein secretion measured. Next generation sequencing was performed on EXOs from rat quiescent and aHSCs and human aHSCs. aHSCs were transfected with siRNA against ectodysplasin-A (EDA), EXOs collected, and their effect on macrophage function analyzed. Human cirrhotic liver was analyzed for EDA mRNA expression and compared to non-tumor liver (NTL). Transfection with large RNA from aHSC-EXOs stimulated macrophage IL-6 and TNFα mRNA expression and protein secretion. EDA mRNA was highly expressed in aHSCs and transfection of aHSCs with EDA-siRNA decreased aHSC-EXO EDA mRNA and blunted the effect of aHSC-EXOs on macrophage function (IL-6/TNFα expression and macrophage migration). Human cirrhotic liver exhibited high EDA mRNA compared to NTL. HSC activation leads to altered EXO mRNA/miRNA profiles with aHSC-EXOs mRNAs exerting a dominant role in altering macrophage function. Ectodysplasin-A mRNA is an important component in aHSC-EXOs in regulating macrophage function.
Identifiants
pubmed: 35964664
pii: S0014-4827(22)00290-7
doi: 10.1016/j.yexcr.2022.113297
pii:
doi:
Substances chimiques
EDAR protein, human
0
Ectodysplasins
0
Edar Receptor
0
Interleukin-6
0
RNA, Messenger
0
RNA, Small Interfering
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113297Subventions
Organisme : NIAAA NIH HHS
ID : R21 AA025429
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors have no disclosures to report.