Regulation of Matrix Metalloproteinase 2 Expression by an Adenosine A1 Agonist in Trabecular Meshwork Cells
10.3341/jkos.2018.59.10.946
- Author:
Min Ju BAEK
1
;
Keun Hae KIM
;
Jae Woo KIM
Author Information
1. Department of Ophthalmology, Daegu Catholic University School of Medicine, Daegu, Korea. jwkim@cu.ac.kr
- Publication Type:Original Article
- Keywords:
Adenosine A1 agonist;
Matrix metalloproteinase 2;
Permeability;
Trabecular meshwork
- MeSH:
Adenosine;
Blotting, Western;
Humans;
Matrix Metalloproteinase 14;
Matrix Metalloproteinase 2;
Permeability;
RNA, Messenger;
Tissue Inhibitor of Metalloproteinase-2;
Trabecular Meshwork
- From:Journal of the Korean Ophthalmological Society
2018;59(10):946-952
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: We investigated the extent of adenosine A1 agonist-induced expression and regulation of matrix metalloproteinase 2 (MMP-2) synthesis in human trabecular meshwork cells (HTMC). METHODS: Primary HTMC cultures were exposed to 0.1 or 1.0 µM N6-cyclohexyladenosine (CHA) for 2 h in the presence or absence of an inhibitor thereof, 8-cyclopentyl-1,3-dimethylxanthine (CPT). The expression level of mRNA encoding MMP-2 was assessed via reverse transcription-polymerase chain reaction, and the levels of tissue inhibitor of metalloproteinase 2 (TIMP2) and membrane-type-1 MMP (MT1-MMP) measured by Western blotting. The permeability of the HTMC monolayer was assessed with the aid of carboxyfluorescein. RESULTS: CHA at 1.0 µM increased the permeability of the HTMC monolayer (p = 0.003) and CHA at both 0.1 and 1.0 µM significantly increased MMP-2 mRNA expression, which was inhibited by co-exposure to CPT (all p < 0.05). CHA increased MMP-2 activity, decreased that of TIMP2, and increased that of MT1-MMP (all p < 0.05). CONCLUSIONS: CHA increased the permeability of the HTMC monolayer and increased MMP-2 activity, decreased TIMP2 activity, and increased MT1-MMP activity. Thus, regulation of TIMP2 and MT1-MMP expression may be involved in the adenosine A1 agonist-induced increase in MMP-2 activity.
