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KMID : 0360220180590100946
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Journal of the Korean Ophthalmological Society
2018 Volume.59 No. 10 p.946 ~ p.952
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Regulation of Matrix Metalloproteinase 2 Expression by an Adenosine A1 Agonist in Trabecular Meshwork Cells
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Baek Min-Ju
Kim Keun-Hae
Kim Jae-Woo
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Abstract
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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.
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KEYWORD
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Adenosine A1 agonist, Matrix metalloproteinase 2, Permeability, Trabecular meshwor
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