Abstract
Abstract: :
Purpose: Posterior capsule opacification (PCO) is caused by proliferation and migration of lens epithelial cells remained after cataract surgery. It has been known that the various cytokines are involved in the proliferation of lens epithelial cells. In this study, we investigated the role of HGF in lens epithelial cells and the signaling pathways that contribute to HGF–induced proliferation. Methods: Capsular–bags prepared from porcine eyes were maintained in serum–free DMEM. The human lens epithelial B3 cells (HLE B3) and rat lens epithelial explants were cultured in MEM supplemented with 20% FCS and Medium 199 with Earle’s salts supplemented with 0.1% BSA, respectively. The cell proliferation was determined by MTT assay, PCNA expression or flow cytometric analysis. The antisense oligonucleotide was used to inhibit the cyclin D1 expression. Activation of MAPKs and PI3K pathway was detected by western blot analysis. Results: HGF induced the proliferation of lens epithelial cells and HGF–stimulated proliferation was significantly inhibited by the treatment with neutralizing c–Met antibody in capsular–bag culture. Studies of the signaling pathway used by HGF in lens epithelial cells to induce proliferation revealed that HGF activates the MAP kinases, ERK and JNK/SAPK, but not p38. Activation of both ERK and JNK/SAPK is required for the HGF–stimulated induction of cyclin D1, which is necessary for the HGF–induced proliferation of lens epithelial cells. PI3K also participated in the regulation of cyclin D1 expression as the upstream of ERK and JNK/SAPK. Conclusions: Taken together, our data indicate that HGF may be a potent growth factor for the lens epithelial cells and contribute the development of PCO, and suggest that the signaling pathway involved in HGF–stimulated proliferation is a potential therapeutic target for PCO.
Keywords: posterior capsular opacification (PCO) • proliferation • signal transduction