J Korean Ophthalmol Soc > Volume 59(10); 2018 > Article
Journal of the Korean Ophthalmological Society 2018;59(10):946-952.
DOI: https://doi.org/10.3341/jkos.2018.59.10.946    Published online October 15, 2018.
Regulation of Matrix Metalloproteinase 2 Expression by an Adenosine A1 Agonist in Trabecular Meshwork Cells.
Min Ju Baek, Keun Hae Kim, Jae Woo Kim
Department of Ophthalmology, Daegu Catholic University School of Medicine, Daegu, Korea. jwkim@cu.ac.kr
섬유주세포에서 아데노신 A1 길항제에 의한 기질단백분해효소 2의 발현 조절
백민주⋅김근해⋅김재우
대구가톨릭대학교 의과대학 안과학교실
Correspondence:  Jae Woo Kim,
Email: jwkim@cu.ac.kr
Received: 30 November 2017   • Revised: 12 December 2017   • Accepted: 28 September 2018
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.
Key Words: Adenosine A1 agonist;Matrix metalloproteinase 2;Permeability;Trabecular meshwork


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