Role of TGF-β1/SMADs signalling pathway in resveratrol-induced reduction of extracellular matrix deposition by dexamethasonetreated human trabecular meshwork cells

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Amy Suzana Abu Bakar Norhafiza Razali Renu Agarwal Igor Iezhitsa Maxim A. Perfilev Pavel M. Vassiliev
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제28권 제4호, 345~359쪽, 전체 15쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2024.07.01

국문 초록

Deposition of extracellular matrix (ECM) in the trabecular meshwork (TM) increases aqueous humour outflow resistance leading to elevation of intraocular pressure (IOP) in primary open-angle glaucoma, which remains the only modifiable risk factor. Resveratrol has been shown to counteract the steroid-induced increase in IOP and increase the TM expression of ECM proteolytic enzymes; however, its effects on the deposition of ECM components by TM and its associated pathways, such as TGF-β-SMAD signalling remain uncertain. This study, therefore, explored the effects of trans-resveratrol on the expression of ECM components, SMAD signalling molecules, plasminogen activator inhibitor-1 and tissue plasminogen activator in dexamethasone-treated human TM cells (HTMCs). We also studied the nature of molecular interaction of trans -resveratrol with SMAD4 domains using ensemble docking. Treatment of HTMCs with 12.5 µM trans-resveratrol downregulated the dexamethasone-induced increase in collagen, fibronectin and α-smooth muscle actin at gene and protein levels through downregulation of TGF-β1, SMAD4, and upregulation of SMAD7. Downregulation of TGF-β1 signalling by trans-resveratrol could be attributed to its effect on the transcriptional activity due to high affinity for the MH2 domain of SMAD4. These effects may contribute to resveratrol's IOP-lowering properties by reducing ECM deposition and enhancing aqueous humour outflow in the TM.

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키워드

Dexamethasone Extracellular matrix Glaucoma Resveratrol Trabecular neshwork