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Effect of Endothelin-1 on proliferation,migration and fibrogenic gene expression in human RPE cells
Affiliation:1. Investigational Toxicology, GDD-GED-Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany;2. Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, 02115 Boston, MA, United States;3. Pathology, GDD-GED-Toxicology, Bayer Pharma AG, 13353 Berlin, Germany;4. Indication Expansion, GDD-GTRG-Cross Indication Platform, Bayer Pharma AG, 13353 Berlin, Germany
Abstract:The pathology of the fibrotic proliferative vitreoretinopathy (PVR) membrane represents an excessive wound healing response characterised by cells’ proliferation, migration and secretion of extracellular matrix molecules (ECMs). Retinal pigment epithelial (RPE) cells are a major cellular component of the fibrotic membrane. Endothelin-1 (ET-1) has been reported to be involved in the development of PVR in vivo research. However, little is known about the role of ET-1 in RPE cells in vitro. In the present study, we investigated the role of ET-1 in the proliferation, migration and secretion of ECMs (such as type I collagen and fibronectin) in RPE cells in vitro. Our results illustrated that ET-1 promoted the proliferation, migration and secretion of ECMs through the protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) signaling pathways in RPE cells in vitro. These findings strongly suggested that ET-1 may play a vital role in the development of PVR.
Keywords:Endothelin-1  Proliferative vitreoretinopathy  Type I collagen  Fibronectin
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