PMID- 22275073
OWN - NLM
STAT- MEDLINE
DCOM- 20121011
LR  - 20211021
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 113
IP  - 4
DP  - 2012 Apr
TI  - Matrix metalloproteinase-9 in homocysteine-induced intestinal microvascular 
      endothelial paracellular and transcellular permeability.
PG  - 1159-69
LID - 10.1002/jcb.23451 [doi]
AB  - Although elevated levels of homocysteine (Hcy), known as hyperhomocysteinemia 
      (HHcy), is associated with inflammatory bowel disease (IBD), the mechanism of Hcy 
      action is unclear. In the present study, we tested the hypothesis that HHcy 
      activates matrix metalloproteinase-9 (MMP-9), which in turn enhances permeability 
      of human intestinal microvascular endothelial cell (HIMEC) layer by decreasing 
      expression of endothelial junction proteins and increasing caveolae formation. 
      HIMECs were grown in Transwells and treated with 500 microM Hcy in the presence or 
      absence of MMP-9 activity inhibitor. Hcy-induced permeability to FITC-conjugated 
      bovine serum albumin (FITC-BSA) was assessed by measuring fluorescence intensity 
      of solutes in the Transwells' lower chambers. The cell-cell interaction and cell 
      barrier function was estimated by measuring trans-endothelial electrical 
      impedance. Confocal microscopy and flow cytometry were used to study cell 
      junction protein expressions. Hcy-induced changes in transcellular transport of 
      HIMECs were estimated by observing formation of functional caveolae defined as 
      caveolae labeled by cholera toxin and antibody against caveolin-1 and one that 
      have taken up FITC-BSA. Hcy instigated HIMEC monolayer permeability through 
      activation of MMP-9. The increased paracellular permeability was associated with 
      degradation of vascular endothelial cadherin and zona occludin-1 and 
      transcellular permeability through increased caveolae formation in HIMECs. 
      Elevation of Hcy content increases permeability of HIMEC layer affecting both 
      paracellular and transcellular transport pathways, and this increased 
      permeability was alleviated by inhibition of MMP-9 activity. These findings 
      contribute to clarification of mechanisms of IBD development.
CI  - (c) 2011 Wiley Periodicals, Inc.
FAU - Munjal, Charu
AU  - Munjal C
AD  - Department of Physiology and Biophysics, University of Louisville School of 
      Medicine, Louisville, KY 40202, USA.
FAU - Tyagi, Neetu
AU  - Tyagi N
FAU - Lominadze, David
AU  - Lominadze D
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - HL-80394/HL/NHLBI NIH HHS/United States
GR  - R01 HL080394/HL/NHLBI NIH HHS/United States
GR  - R01 NS051568-05/NS/NINDS NIH HHS/United States
GR  - R01 HL071010/HL/NHLBI NIH HHS/United States
GR  - R01 NS051568/NS/NINDS NIH HHS/United States
GR  - NS-51568/NS/NINDS NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
GR  - HL-71010/HL/NHLBI NIH HHS/United States
GR  - R01 HL074185/HL/NHLBI NIH HHS/United States
GR  - R01 HL071010-08/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Actins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (TJP1 protein, human)
RN  - 0 (Zonula Occludens-1 Protein)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Actins/biosynthesis
MH  - Cells, Cultured
MH  - Endothelium, Vascular/enzymology/*metabolism
MH  - Enzyme Activation
MH  - Flow Cytometry
MH  - Homocysteine/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Intestines/*blood supply/enzymology
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Membrane Proteins/metabolism
MH  - Microvessels/enzymology/*metabolism
MH  - Permeability
MH  - Phosphoproteins/metabolism
MH  - Tight Junctions
MH  - Zonula Occludens-1 Protein
PMC - PMC3337944
MID - NIHMS342134
EDAT- 2012/01/26 06:00
MHDA- 2012/10/12 06:00
PMCR- 2013/04/01
CRDT- 2012/01/26 06:00
PHST- 2012/01/26 06:00 [entrez]
PHST- 2012/01/26 06:00 [pubmed]
PHST- 2012/10/12 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - 10.1002/jcb.23451 [doi]
PST - ppublish
SO  - J Cell Biochem. 2012 Apr;113(4):1159-69. doi: 10.1002/jcb.23451.