FGF-2 Differentially Regulates Lens Epithelial Cell Behaviour during TGF-β-Induced EMT

Area of Science:

• Ophthalmology
• Cell Biology
• Developmental Biology

Background:

• Lens epithelial cell (LEC) behavior is regulated by fibroblast growth factor (FGF) and transforming growth factor-beta (TGF-β).
• The interplay between FGF and TGF-β influences lens cell fate in a dose-dependent manner.
• Understanding these interactions is crucial for addressing lens pathologies like posterior capsular opacification (PCO).

Purpose of the Study:

• To investigate how a fiber-differentiating dose of FGF-2 differentially affects lens epithelial cells (LECs) undergoing TGF-β2-induced epithelial-mesenchymal transition (EMT).
• To compare the responses of central LECs (CLECs) and peripheral LECs (PLECs) to combined FGF-2 and TGF-β2 treatment.

Main Methods:

• Postnatal rat lens epithelial explants were cultured for 7 days with FGF-2 (200 ng/mL) and/or TGF-β2 (50 pg/mL).
• Immunolabeling was used to assess markers for EMT (α-SMA), lens fiber differentiation (β-crystallin), cell adhesion (β-catenin), and cytoskeleton (alpha-tropomyosin).
• Smad2/3 and MAPK/ERK1/2 signaling pathways were analyzed.

Main Results:

• Combined FGF-2 and TGF-β2 treatment induced differential responses: CLECs underwent EMT (α-SMA positive, β-crystallin negative), while PLECs showed signs of fiber differentiation (β-crystallin positive, α-SMA negative).
• Compared to TGF-β2 alone, α-SMA expression was significantly decreased in CLECs co-treated with FGF-2 and TGF-β2.
• CLECs exhibited increased Smad2/3 signaling, whereas PLECs showed more pronounced ERK1/2 signaling.

Conclusions:

• FGF-2 differentially regulates LEC behavior during TGF-β2-induced EMT, creating a heterogeneous cell population.
• This differential response mirrors cellular changes observed in posterior capsular opacification (PCO) development.
• The cooperative interaction between FGF and TGF-β contributes to lens pathology, offering insights into PCO prevention.