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Published on: August 20, 2016
Effect of MT1-MMP deficiency and overexpression in corneal keratocytes on vascular endothelial cell migration and
Dimitri T Azar1, Fabio H Casanova, Tatsuya Mimura
1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois 60612, USA. dazar@uic.edu
Purpose:
To determine the effect of keratocyte-derived MT1-MMP on calf pulmonary artery endothelial cell (CPAE) proliferation and migration.
Methods:
Keratocyte lines were generated from MT1-MMP knockout (KO) and wild type (WT) mice. WT keratocytes were transfected with WT or mutant MT1-MMP DNAs (DeltaTC or E240A). The effect of keratocyte-conditioned media on CPAE proliferation and migration was assayed.
Results:
KO keratocyte conditioned media resulted in the greatest increase of CPAE cell proliferation (190.5+/-6.0%; p<0.01). WT keratocyte conditioned media showed higher CPAE proliferation (155.4+/-3.6%) than WT/MT1-MMP-transfected keratocytes (119.7+/-2.2%; p<0.001). Migration assays confirmed these findings.
Conclusions:
Keratocyte-derived MT1-MMP has anti-angiogenic effects in CPAE cells.
Insights
Keratocyte-derived MT1-MMP inhibits calf pulmonary artery endothelial cell (CPAE) proliferation and migration, suggesting anti-angiogenic properties. This research impacts understanding of blood vessel formation and related conditions.
Area of Science:
- Cell Biology
- Biochemistry
- Angiogenesis Research
Background:
- Matrix metalloproteinase 1 (MT1-MMP) plays a role in extracellular matrix remodeling.
- Endothelial cell proliferation and migration are crucial for angiogenesis.
- Keratocytes are connective tissue cells that can influence their microenvironment.
Purpose of the Study:
- To investigate the impact of keratocyte-derived MT1-MMP on the proliferation and migration of calf pulmonary artery endothelial cells (CPAE).
Main Methods:
- Generated keratocyte cell lines from MT1-MMP knockout (KO) and wild-type (WT) mice.
- Transfected WT keratocytes with WT or mutant MT1-MMP DNA.
- Assayed the effect of conditioned media from these keratocytes on CPAE cell proliferation and migration.
Main Results:
- Conditioned media from KO keratocytes significantly increased CPAE cell proliferation (190.5%).
- WT keratocyte conditioned media showed higher CPAE proliferation (155.4%) compared to media from MT1-MMP-transfected keratocytes (119.7%).
- Migration assays corroborated the observed effects on proliferation.
Conclusions:
- Keratocyte-derived MT1-MMP exhibits anti-angiogenic effects on CPAE cells.
- MT1-MMP expression in keratocytes influences endothelial cell behavior.
- These findings contribute to understanding MT1-MMP's role in vascular biology.
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