The role of TRAF6 in regulating MAP3K7/P38/MAPK pathway in the epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is a major cause of blindness. Surgery remains the primary clinical intervention, but its outcomes are frequently unsatisfactory. A deeper understanding of PVR pathophysiology is therefore essential for developing new treatments. TRAF6 is a multifunctional intracellular adaptor protein that regulates diverse biological processes, yet its role in PVR is unknown. Here, we investigated the function of TRAF6 in PVR and its downstream mechanisms using a mouse model and ARPE-19 cells. The results demonstrated that TRAF6 expression was upregulated in the retinas of PVR model mice and in ARPE-19 cells. Knockdown of TRAF6 alleviated PVR progression in mice by suppressing inflammation and the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. Conversely, TRAF6 overexpression in ARPE-19 cells exacerbated TGF-β1-induced EMT. Mechanistically, TRAF6 positively regulated MAP3K7 expression via a protein-protein interaction. Knockdown of TRAF6 inhibited P38/MAPK signaling pathway activation by reducing MAP3K7 expression. Furthermore, knockdown of TRAF6 attenuated the promoting effect of MAP3K7 overexpression on TGF-β1-induced EMT in RPE cells. In conclusion, TRAF6 knockdown protects against PVR in mice by inhibiting the MAP3K7 and p38 MAPK pathways.