Role of TGF-β1/SMADs signalling pathway in resveratrol-induced reduction of extracellular matrix deposition by dexamethasone-treated human trabecular meshwork cells
10.4196/kjpp.2024.28.4.345
- Author:
Amy Suzana Abu BAKAR
1
;
Norhafiza RAZALI
;
Renu AGARWAL
;
Igor IEZHITSA
;
Maxim A. PERFILEV
;
Pavel M. VASSILIEV
Author Information
1. Department of Pharmacology, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, 47000 Sungai Buloh, Selangor, Malaysia
- Publication Type:Original Article
- From:The Korean Journal of Physiology and Pharmacology
2024;28(4):345-359
- CountryRepublic of Korea
- Language:EN
-
Abstract:
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.
