Characterization of TGF-β by Induced Oxidative Stress in Human Trabecular Meshwork Cells

Area of Science:

• Cell Biology
• Ophthalmology
• Molecular Biology

Background:

• Oxidative stress from reactive oxygen species (ROS) is implicated in glaucoma pathogenesis, causing damage to human trabecular meshwork cells (HTMCs).
• The transforming growth factor-β (TGF-β) signaling pathway is known to influence extracellular matrix (ECM) fibrosis and cellular antioxidant responses under oxidative stress.

Purpose of the Study:

• To investigate the dual roles and regulatory mechanisms of TGF-β in HTMCs subjected to oxidative stress.
• To elucidate the specific signaling pathways involved in TGF-β's protective effects against hydrogen peroxide (H₂O₂)-induced injury.

Main Methods:

• An in vitro oxidative stress model was established using H₂O₂ on HTMCs.
• TGF-β1 and TGF-β2 roles were assessed via knockdown (shTGF-β1, shTGF-β2) and recombinant protein (rhTGF-β1) treatments.
• Protein levels (p38 MAPK, SMADs, AKT), cell apoptosis, ROS levels, and actin cytoskeleton structure were analyzed.

Main Results:

• H₂O₂ stimulation activated p38 MAPK, TGF-β, and SMAD signaling pathways in HTMCs.
• Pretreatment with low-concentration rhTGF-β1 (1 ng/mL) reduced HTMC apoptosis and ROS levels, enhancing cell survival.
• TGF-β1 and TGF-β2 were linked to antioxidant signaling, activating fibrosis-related proteins like collagen I and laminin.

Conclusions:

• Low concentrations of TGF-β1 exert a protective effect on HTMCs against oxidative stress-induced damage.
• This protection is mediated by maintaining a balance in p-p38 MAPK and p-AKT signaling pathways.
• The findings present a novel signaling transduction mechanism for TGF-β1 in therapeutic strategies for HTMC oxidative stress.