J Korean Ophthalmol Soc.  2018 Oct;59(10):946-952. 10.3341/jkos.2018.59.10.946.

Regulation of Matrix Metalloproteinase 2 Expression by an Adenosine A1 Agonist in Trabecular Meshwork Cells

Affiliations
  • 1Department of Ophthalmology, Daegu Catholic University School of Medicine, Daegu, Korea. jwkim@cu.ac.kr

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.

Keyword

Adenosine A1 agonist; Matrix metalloproteinase 2; Permeability; Trabecular meshwork

MeSH Terms

Adenosine*
Blotting, Western
Humans
Matrix Metalloproteinase 14
Matrix Metalloproteinase 2*
Permeability
RNA, Messenger
Tissue Inhibitor of Metalloproteinase-2
Trabecular Meshwork*
Adenosine
Matrix Metalloproteinase 14
Matrix Metalloproteinase 2
RNA, Messenger
Tissue Inhibitor of Metalloproteinase-2
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