A HGF-derived peptide suppresses EMT in human lens epithelial cells via the TGF-β/Smad and Akt/mTOR signaling pathways

Posterior capsule opacification (PCO) as a result of proliferation and fibrogenesis of lens epithelial cells (LECs) is the most frequent long-term complication of modern cataract surgery. LECs may undergo epithelial-mesenchymal transition (EMT) that resembles the morphological and molecular characteristics of PCO. A pre-identified novel, hepatocyte growth factor (HGF)-derived peptide H-RN, was reported to exhibit anti-angiogenic activity and anti-inflammatory effects in ocular cells bothin vitroandin vivo. However, the role of H-RN in the promotion of the development of EMT in LECs is unknown. In the present study, the effects of H-RN on the development of EMT induced by transforming growth factor (TGF)-beta in human LECs, and the possible signaling pathways participating in this process were investigated. The results showed that H-RN promoted the expression of the EMT-associated markers, alpha-smooth muscle actin and fibronectin, whereas the expression of E-cadherin and connexin 43 were reduced. The morphological changes typically associated with EMT seen in LECs induced by TGF-beta 2 were inhibited by H-RN, which was consistent with the effects of a TGF-beta 2 inhibitor, SB431542. Smad2 and Smad3 phosphorylation induced by TGF-beta 2 were reduced by H-RN, and phosphorylation of Akt, mTOR and P70S6K induced by TGF-beta 2 were also notably reduced by H-RN in LECs. Therefore, the results of the present study showed that H-RN treatment significantly suppressed the development of EMT induced by TGF-beta 2, at least partially through the TGF-beta/Smad and Akt/mTOR signaling pathways in human LECs. The present study highlights that H-RN, a novel HGF-derived peptide, may be a novel therapeutic agent for prevention and treatment of PCO.