PMID- 33513427
OWN - NLM
STAT- MEDLINE
DCOM- 20210910
LR  - 20220503
IS  - 1879-260X (Electronic)
IS  - 0925-4439 (Print)
IS  - 0925-4439 (Linking)
VI  - 1867
IP  - 5
DP  - 2021 May 1
TI  - Deletion of Mcpip1 in Mcpip1(fl/fl)Alb(Cre) mice recapitulates the phenotype of 
      human primary biliary cholangitis.
PG  - 166086
LID - S0925-4439(21)00019-3 [pii]
LID - 10.1016/j.bbadis.2021.166086 [doi]
AB  - Primary biliary cholangitis (PBC) is an autoimmune disease characterized by 
      progressive destruction of the intrahepatic bile ducts. The immunopathology of 
      PBC involves excessive inflammation; therefore, negative regulators of 
      inflammatory response, such as Monocyte Chemoattractant Protein-1-Induced 
      Protein-1 (MCPIP1) may play important roles in the development of PBC. The aim of 
      this work was to verify whether Mcpip1 expression protects against development of 
      PBC. Genetic deletion of Zc3h12a was used to characterize the role of Mcpip1 in 
      the pathogenesis of PBC in 6-52-week-old mice. We found that Mcpip1 deficiency in 
      the liver (Mcpip1(fl/fl)Alb(Cre)) recapitulates most of the features of human 
      PBC, in contrast to mice with Mcpip1 deficiency in myeloid cells 
      (Mcpip1(fl/fl)LysM(Cre) mice), which present with robust myeloid cell-driven 
      systemic inflammation. In Mcpip1(fl/fl)Alb(Cre) livers, intrahepatic bile ducts 
      displayed proliferative changes with inflammatory infiltration, bile duct 
      destruction, and fibrosis leading to cholestasis. In plasma, increased 
      concentrations of IgG, IgM, and AMA autoantibodies (anti-PDC-E2) were detected. 
      Interestingly, the phenotype of Mcpip1(fl/fl)Alb(Cre) mice was robust in 
      6-week-old, but milder in 12-24-week-old mice. Hepatic transcriptome analysis of 
      6-week-old and 24-week-old Mcpip1(fl/fl)Alb(Cre) mice showed 812 and 8 
      differentially expressed genes, respectively, compared with age-matched control 
      mice, and revealed a distinct set of genes compared to those previously 
      associated with development of PBC. In conclusion, Mcpip1(fl/fl)Alb(Cre) mice 
      display early postnatal phenotype that recapitulates most of the features of 
      human PBC.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Kotlinowski, Jerzy
AU  - Kotlinowski J
AD  - Department of General Biochemistry, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland. 
      Electronic address: j.kotlinowski@uj.edu.pl.
FAU - Hutsch, Tomasz
AU  - Hutsch T
AD  - Department of Experimental Physiology and Pathophysiology, Laboratory of Centre 
      for Preclinical Research, Medical University of Warsaw, Pawinskiego 3c, 02-106 
      Warsaw, Poland; Veterinary Diagnostic Laboratory ALAB bioscience, Stepinska 
      22/30, 00-739 Warszawa, Poland.
FAU - Czyzynska-Cichon, Izabela
AU  - Czyzynska-Cichon I
AD  - Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian 
      University, Bobrzynskiego 14, 30-348 Krakow, Poland.
FAU - Wadowska, Marta
AU  - Wadowska M
AD  - Department of Microbiology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
FAU - Pydyn, Natalia
AU  - Pydyn N
AD  - Department of General Biochemistry, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
FAU - Jasztal, Agnieszka
AU  - Jasztal A
AD  - Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian 
      University, Bobrzynskiego 14, 30-348 Krakow, Poland.
FAU - Kij, Agnieszka
AU  - Kij A
AD  - Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian 
      University, Bobrzynskiego 14, 30-348 Krakow, Poland.
FAU - Dobosz, Ewelina
AU  - Dobosz E
AD  - Department of Microbiology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
FAU - Lech, Maciej
AU  - Lech M
AD  - Department of Microbiology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland; 
      Department of Medicine IV, LMU Hospital, Munich, Germany.
FAU - Miekus, Katarzyna
AU  - Miekus K
AD  - Department of General Biochemistry, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
FAU - Pospiech, Ewelina
AU  - Pospiech E
AD  - Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
FAU - Fu, Mingui
AU  - Fu M
AD  - Department of Biomedical Science and Shock/Trauma Research Center, School of 
      Medicine, University of Missouri-Kansas City, Kansas City, USA.
FAU - Jura, Jolanta
AU  - Jura J
AD  - Department of General Biochemistry, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
FAU - Koziel, Joanna
AU  - Koziel J
AD  - Department of Microbiology, Faculty of Biochemistry, Biophysics and 
      Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
FAU - Chlopicki, Stefan
AU  - Chlopicki S
AD  - Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian 
      University, Bobrzynskiego 14, 30-348 Krakow, Poland; Chair of Pharmacology, 
      Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Krakow, Poland.
LA  - eng
GR  - R15 AI138116/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210126
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulins)
RN  - EC 3.1.- (Ribonucleases)
RN  - EC 3.1.- (Zc3h12a protein, mouse)
SB  - IM
MH  - Animals
MH  - Autoantibodies/*immunology
MH  - Female
MH  - Immunoglobulins/*immunology
MH  - Inflammation/etiology/metabolism/*pathology
MH  - Liver Cirrhosis/etiology/metabolism/*pathology
MH  - Liver Cirrhosis, Biliary/etiology/metabolism/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - *Phenotype
MH  - Ribonucleases/*physiology
PMC - PMC8938941
MID - NIHMS1779517
OTO - NOTNLM
OT  - Autoimmune disease
OT  - Inflammation
OT  - MCPIP1
OT  - Primary biliary cholangitis
OT  - Regnase1
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/01/30 06:00
MHDA- 2021/09/11 06:00
PMCR- 2022/05/01
CRDT- 2021/01/29 20:06
PHST- 2020/09/04 00:00 [received]
PHST- 2021/01/19 00:00 [revised]
PHST- 2021/01/21 00:00 [accepted]
PHST- 2021/01/30 06:00 [pubmed]
PHST- 2021/09/11 06:00 [medline]
PHST- 2021/01/29 20:06 [entrez]
PHST- 2022/05/01 00:00 [pmc-release]
AID - S0925-4439(21)00019-3 [pii]
AID - 10.1016/j.bbadis.2021.166086 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2021 May 1;1867(5):166086. doi: 
      10.1016/j.bbadis.2021.166086. Epub 2021 Jan 26.