PMID- 23886643
OWN - NLM
STAT- MEDLINE
DCOM- 20140624
LR  - 20131106
IS  - 1422-6421 (Electronic)
IS  - 1422-6405 (Linking)
VI  - 198
IP  - 2
DP  - 2013
TI  - Bone marrow mononuclear cell transplantation increases metalloproteinase-9 and 13 
      and decreases tissue inhibitors of metalloproteinase-1 and 2 expression in the 
      liver of cholestatic rats.
PG  - 139-48
LID - 10.1159/000353215 [doi]
AB  - Liver fibrosis results from chronic injury followed by activation of macrophages 
      and fibrogenic cells like myofibroblasts and activated hepatic stellate cells. 
      These fibrogenic cells express alpha-smooth muscle actin (alpha-SMA) and produce 
      excessive extracellular matrix (ECM), with disorganization and loss of function 
      of hepatic parenchyma. It is known that increased levels of metalloproteinases 
      (MMPs) in liver fibrosis are associated with reduction of the pathologic ECM and 
      fibrosis resolution. Recently, it has been shown that bone marrow mononuclear 
      cells (BMMNCs) may reduce collagen and alpha-SMA expression, and ameliorate liver 
      function in cholestatic rats. Therefore, this study aimed to analyze MMP-2, MMP-9 
      and MMP-13, and tissue inhibitors of MMPs (TIMPs)-1 and TIMP-2 in the liver of 
      cholestatic rats transplanted with BMMNC. Animals were divided into normal rats, 
      cholestatic rats obtained after 14 and 21 days of bile duct ligation (BDL), and 
      rats obtained after 14 days of BDL that received BMMNCs and were killed after 7 
      days. MMP and TIMP expression was assessed by Western blotting, along with alpha-SMA, 
      CD68 and CD11b expression by confocal microscopy. Western blotting analysis 
      showed that 14-day BDL animals had significantly reduced amounts of MMP-2 and 
      MMP-13, but increased amounts of MMP-9 compared to normal rats. After 21 days of 
      BDL, overall MMP amounts were decreased and TIMPs were increased. BMMNC 
      transplantation significantly increased MMP-9 and MMP-13, and decreased TIMP 
      expression. Increased MMP activity was confirmed by zymography. MMP-9 and MMP-13 
      were expressed by macrophages near fibrotic septa, suggesting BMMNC may stimulate 
      MMP production in fibrotic livers, contributing to ECM degradation and hepatic 
      regeneration.
CI  - (c) 2013 S. Karger AG, Basel.
FAU - Nunes de Carvalho, Simone
AU  - Nunes de Carvalho S
AD  - Laboratorio Cultura de Celulas, Departamento de Histologia e Embriologia, 
      Instituto de Biologia, Universidade do Estado do Rio de Janeiro, UERJ, Rio de 
      Janeiro, Brazil.
FAU - Helal-Neto, Edward
AU  - Helal-Neto E
FAU - de Andrade, Daniela Caldas
AU  - de Andrade DC
FAU - Costa Cortez, Erika Afonso
AU  - Costa Cortez EA
FAU - Thole, Alessandra Alves
AU  - Thole AA
FAU - Barja-Fidalgo, Christina
AU  - Barja-Fidalgo C
FAU - de Carvalho, Lais
AU  - de Carvalho L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130724
PL  - Switzerland
TA  - Cells Tissues Organs
JT  - Cells, tissues, organs
JID - 100883360
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Bone Marrow Cells
MH  - *Bone Marrow Transplantation
MH  - Cholestasis/*enzymology/pathology/therapy
MH  - Fluorescent Antibody Technique
MH  - Liver/*enzymology/pathology
MH  - Male
MH  - Matrix Metalloproteinase 13/*metabolism
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Microscopy, Confocal
MH  - Rats
MH  - Rats, Wistar
MH  - Tissue Inhibitor of Metalloproteinase-1/*metabolism
MH  - Tissue Inhibitor of Metalloproteinase-2/*metabolism
EDAT- 2013/07/28 06:00
MHDA- 2014/06/25 06:00
CRDT- 2013/07/27 06:00
PHST- 2013/05/21 00:00 [accepted]
PHST- 2013/07/27 06:00 [entrez]
PHST- 2013/07/28 06:00 [pubmed]
PHST- 2014/06/25 06:00 [medline]
AID - 000353215 [pii]
AID - 10.1159/000353215 [doi]
PST - ppublish
SO  - Cells Tissues Organs. 2013;198(2):139-48. doi: 10.1159/000353215. Epub 2013 Jul 
      24.