Downregulation of COL12A1 and COL13A1 by a selective EP2 receptor agonist, omidenepag, in human trabecular meshwork cells

被引:5
作者
Kumon, Masashi [1 ]
Fuwa, Masahiro [1 ]
Shimazaki, Atsushi [1 ]
Odani-Kawabata, Noriko [2 ]
Iwamura, Ryo [3 ]
Yoneda, Kenji [3 ]
Kato, Masatomo [1 ]
机构
[1] Santen Pharmaceut Co Ltd, Prod Dev Div, Nara, Japan
[2] Santen Pharmaceut Co Ltd, Prod Dev Div, Osaka, Japan
[3] UBE Corp, Div Pharmaceut, Pharmaceut Res Lab, Yamaguchi, Japan
来源
PLOS ONE | 2023年 / 18卷 / 01期
关键词
EXTRACELLULAR-MATRIX; INTRAOCULAR-PRESSURE; XII COLLAGEN; GLAUCOMA; EXPRESSION; OUTFLOW; COMPONENT; ISOPROPYL; CULTURE; TISSUE;
D O I
10.1371/journal.pone.0280331
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Omidenepag isopropyl (OMDI) is an intraocular pressure (IOP)-lowering drug used to treat glaucoma. The active form of OMDI, omidenepag (OMD), lowers elevated IOP, the main risk factor for glaucoma, by increasing the aqueous humor outflow; however, a detailed understanding of this mechanism is lacking. To clarify the IOP-lowering mechanism of OMDI, the effects of OMD on the mRNA expression of the extracellular matrix, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were evaluated in human trabecular meshwork cells. Under 2D culture conditions, the mRNA expression of FN1, COL1A1, COL1A2, COL12A1, and COL13A1 decreased in a concentration-dependent manner after 6 or 24 h treatment with 10 nM, 100 nM, and 1 mu M OMD, while that of COL18A1 decreased after 6 h treatment with 1 mu M OMD. Significant changes in expression were observed for many MMP and TIMP genes. Under 3D culture conditions, the extracellular matrix-related genes COL12A1 and COL13A1 were downregulated by OMD treatment at all three concentrations. Under both 2D and 3D culture conditions, COL12A1 and COL13A1 were downregulated following OMD treatment. Reduction in the extracellular matrix contributes to the decrease in outflow resistance, suggesting that the downregulation of the two related genes may be one of the factors influencing the IOP-lowering effect of OMDI. Our findings provide insights for the use of OMDI in clinical practice.
引用
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页数:17
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