Abstract
Purpose :
In this study, we investigated the role of PAD2-induced citrullination on transforming growth factor-beta (TGF-β) in cultured human human corneal endothelial cells (hCECs).
Methods :
After cells were treated by AMF30a. cell viability, proliferation rate, cell shape, adhesion assay and intracellular oxidative stress levels were measured. Cell cycle analysis were performed using PI staining. Then, cells were treated with or without AMF30a under the stress of TGF-β. Protein levels were evaluated by western blotting. Oxidative stress levels was evaluated.
Results :
PAD2 inhibition increased cell viability, proliferation and adhesion, and promoted the progression of cell cycle. PAD2 inhibition showed the effects on cell morphology, including cell size and elongation factor and altered expression of cytoskeleton proteins, including F-actin and E-cadherin. Intracellular oxidative stress levels were decreased by PAD2 inhibition. PAD2 inhibition suppressed TGF-β-induced senescence, oxidative stress levels and NF-kB translocation through regulating ROCK2/HIPPO pathway.
Conclusions :
In conclusion, PAD2 inhibition promoted the proliferation of hCECs and protect against cellular senescence and cell death induced by TGF-β, suggesting that PAD2 may play an important role in regulating hCEC survival and function. These findings suggest that targeting PAD2 may have therapeutic potential for diseases that involve hCEC dysfunction or damage.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.