Nr2f1 Drives Fibrotic Cataract Formation Through Activation Of Stat3

Cataracts stay 1 of nan astir prevalent and debilitating oculus conditions, often requiring surgical involution to reconstruct sight. Yet moreover aft surgery, galore patients create anterior subcapsular cataracts (ASC), characterized by fibrotic insubstantial maturation beneath nan lens capsule. This complication arises from epithelial-mesenchymal modulation (EMT), a process wherever lens epithelial cells get migratory, fibrotic traits. While transforming maturation factor-beta (TGF-β) is known to thrust this transition, nan downstream molecular mechanisms stay elusive. Emerging grounds suggests that transcription factors for illustration NR2F1 whitethorn play a domiciled successful fibrosis crossed tissues. Due to these challenges, location is simply a pressing request to analyse molecular regulators that thrust EMT and fibrotic cataracts.

In a caller study (DOI: 10.1016/j.gendis.2025.101549) led by scientists astatine Chongqing Medical University and Chongqing General Hospital, researchers uncovered a caller regulatory axis driving cataract-associated fibrosis. The findings, published connected January 28, 2025, successful Genes & Diseases, uncover that NR2F1 promotes fibrosis by straight activating nan STAT3 signaling pathway. Using some TGF-β1-treated quality lens epithelial cells and a rodent exemplary of ASC, nan squad discovered that defective autophagy boosts NR2F1 macromolecule accumulation, fueling compartment decease and fibrotic plaque formation. The investigation not only identifies a caller molecular system down cataract progression but besides highlights imaginable therapeutic targets for intervention.

The researchers began by confirming elevated NR2F1 macromolecule levels successful cataract-affected lens tissues and TGF-β1-stimulated quality lens epithelial cells. While mRNA levels of NR2F1 dropped, its macromolecule levels rose—suggesting post-transcriptional dysregulation. Further investigation revealed that impaired autophagy, a cellular cleanup process, was responsible for NR2F1 macromolecule buildup. Blocking autophagy successful cells mimicked nan TGF-β1 effect, reinforcing this link.

Functionally, silencing NR2F1 dramatically suppressed nan EMT process, reduced look of fibrotic markers (FN1, VIM, α-SMA), and curbed compartment migration and apoptosis. In ASC rodent models, injection of an NR2F1-silencing AAV led to visibly clearer lenses and less fibrotic plaques. Mechanistic experiments revealed that NR2F1 straight binds to nan promoter of STAT3, triggering its phosphorylation and downstream activation.

The squad validated nan value of this relationship by utilizing a p-STAT3 inhibitor, which successfully reduced fibrotic and apoptotic markers. These findings propose that nan NR2F1-STAT3 axis is simply a cardinal driver of fibrosis successful cataract formation, operating done autophagy disruption and transcriptional reprogramming. This dual insight—both mechanistic and therapeutic—provides a promising guidance for combating fibrotic cataracts beyond existent surgical solutions.

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Journal reference:

Zuo, H., et al. (2025). Autophagy-induced NR2F1 activation promotes nan apoptosis of lens epithelial cells and facilitates cataract-associated fibrosis done targeting STAT3. Genes & Diseases. doi.org/10.1016/j.gendis.2025.101549.