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

Abstract

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 both invitro and invivo. 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)‑β 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, α‑smooth muscle actin and fibronectin, whereas the expression of E‑cadherin and connexin43 were reduced. The morphological changes typically associated with EMT seen in LECs induced by TGF‑β2 were inhibited by H‑RN, which was consistent with the effects of a TGF‑β2 inhibitor, SB431542. Smad2 and Smad3 phosphorylation induced by TGF‑β2 were reduced by H‑RN, and phosphorylation of Akt, mTOR and P70S6K induced by TGF‑β2 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‑β2, at least partially through the TGF‑β/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.