PMID- 32887613
OWN - NLM
STAT- MEDLINE
DCOM- 20210909
LR  - 20210909
IS  - 1478-811X (Electronic)
IS  - 1478-811X (Linking)
VI  - 18
IP  - 1
DP  - 2020 Sep 4
TI  - Alpha-1 antitrypsin deficient individuals have circulating extracellular vesicles 
      with profibrogenic cargo.
PG  - 140
LID - 10.1186/s12964-020-00648-0 [doi]
LID - 140
AB  - BACKGROUND: Alpha-1 antitrypsin deficiency (AATD)-mediated liver disease is a 
      toxic "gain-of-function" inflammation in the liver associated with intracellular 
      retention of mutant alpha-1 antitrypsin. The clinical presentation of the disease 
      includes fibrosis, cirrhosis and liver failure. However, the pathogenic mechanism 
      of AATD-mediated liver disease is not well understood. Here, we investigated the 
      role of plasma extracellular vesicles (EVs) in progression of AATD-mediated liver 
      disease. METHODS: EVs were isolated from plasma of AATD individuals with liver 
      disease and healthy controls. Their cytokines and miRNA content were examined by 
      multiplex assay and small RNA sequencing. The bioactivity of EVs was assessed by 
      qPCR, western blot analysis and immunofluorescent experiments using human hepatic 
      stellate cells (HSCs) treated with EVs isolated from control or AATD plasma 
      samples. RESULTS: We have found that AATD individuals have a distinct population 
      of EVs with pathological cytokine and miRNA contents. When HSCs were cultured 
      with AATD plasma derived-EVs, the expression of genes related to the development 
      of fibrosis were significantly amplified compared to those treated with healthy 
      control plasma EVs. CONCLUSION: AATD individuals have a distinct population of 
      EVs with abnormal cytokine and miRNA contents and the capacity to activate HSCs 
      and mediate fibrosis. Better understanding of the components which cause liver 
      inflammation and fibrogenesis, leading to further liver injury, has the potential 
      to lead to the development of new treatments or preventive strategies to prevent 
      AATD-mediated liver disease. Video abstract.
FAU - Khodayari, Nazli
AU  - Khodayari N
AUID- ORCID: 0000-0002-4659-1622
AD  - Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, 
      Gainesville, USA. Nazli.khodayari@medicine.ufl.edu.
FAU - Oshins, Regina
AU  - Oshins R
AD  - Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, 
      Gainesville, USA.
FAU - Holliday, L Shannon
AU  - Holliday LS
AD  - College of Dentistry, University of Florida, Gainesville, USA.
FAU - Clark, Virginia
AU  - Clark V
AD  - Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, 
      Gainesville, USA.
FAU - Xiao, Qiang
AU  - Xiao Q
AD  - MilliporeSigma, Burlington, MO, USA.
FAU - Marek, George
AU  - Marek G
AD  - Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, 
      Gainesville, USA.
FAU - Mehrad, Borna
AU  - Mehrad B
AD  - Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, 
      Gainesville, USA.
FAU - Brantly, Mark
AU  - Brantly M
AD  - Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, 
      Gainesville, USA. Mark.Brantly@medicine.ufl.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200904
PL  - England
TA  - Cell Commun Signal
JT  - Cell communication and signaling : CCS
JID - 101170464
RN  - 0 (Cytokines)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cytokines/analysis
MH  - Extracellular Vesicles/genetics/*pathology
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Liver/metabolism/*pathology
MH  - Liver Cirrhosis/blood/complications/genetics/*pathology
MH  - Male
MH  - MicroRNAs/analysis/genetics
MH  - Middle Aged
MH  - alpha 1-Antitrypsin Deficiency/blood/complications/genetics/*pathology
PMC - PMC7487708
OTO - NOTNLM
OT  - Alpha-1 antitrypsin
OT  - Cytokine
OT  - Extracellular vesicles
OT  - Liver fibrosis
OT  - miRNA
COIS- The authors declare that they have no competing interests.
EDAT- 2020/09/06 06:00
MHDA- 2021/09/10 06:00
PMCR- 2020/09/04
CRDT- 2020/09/05 05:15
PHST- 2020/05/14 00:00 [received]
PHST- 2020/08/15 00:00 [accepted]
PHST- 2020/09/05 05:15 [entrez]
PHST- 2020/09/06 06:00 [pubmed]
PHST- 2021/09/10 06:00 [medline]
PHST- 2020/09/04 00:00 [pmc-release]
AID - 10.1186/s12964-020-00648-0 [pii]
AID - 648 [pii]
AID - 10.1186/s12964-020-00648-0 [doi]
PST - epublish
SO  - Cell Commun Signal. 2020 Sep 4;18(1):140. doi: 10.1186/s12964-020-00648-0.