ERK1/2 pathway mediates epithelial-mesenchymal transition by cross-interacting with TGFβ/Smad and Jagged/Notch signaling pathways in lens epithelial cells
Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is the major pathological mechanism in anterior subcapsular cataract (ASC) and posterior capsule opacification (PCO), which are important causes of visual impairment. Extracellular signal-regulated kinase (ERK)1/2 pathway has been reported to play a major role in carcinogenesis, cancer metastasis and various fibrotic diseases. We hypothesized that ERK1/2 signaling can cross-interact with canonical transforming growth factor β (TGFβ)/Smad signaling and the Notch pathway, which subsequently contributes to LECs EMT. In this study, we demonstrated that ERK1/2 signaling was activated in TGFβ2induced EMT in human LECs, whereas the blockade of TGFβ2/Smad2/3 signaling with SB431542 did not inhibit the activation of ERK1/2 induced by TGFβ2. In addition, inactivation of ERK1/2 signaling with a specific MEK/ERK1/2 inhibitor, U0126, completely prevented the TGFβ2-induced upregulation of α-SMA, collagen type I, collagen type IV and fibronectin. We also demonstrated that inactivation of ERK1/2 signaling inhibited canonical TGFβ/Smad signaling, as well as the Jagged/Notch pathway. By contrast, blockade of the Notch pathway by DAPT inhibited the TGFβ2induced activation of ERK1/2 pathway in LECs. Thus, results of this study provide evidence for the complex interplay between ERK1/2, TGFβ/Smad, and Jagged/Notch signaling pathways in the regulation of EMT in LECs. Inhibition of the ERK1/2 pathway may therefore have therapeutic value in the prevention and treatment of ASC and PCO.
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Document Type: Research Article
Affiliations: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yatsen University, Guangzhou, Guangdong 510060, P.R. China
Publication date: June 1, 2014
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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