Epithelial-to-mesenchymal transition in zebrafish epicardium is associated with inflammatory response during heart regeneration

• Main Authors: Yu, Bo Ting, 余柏廷
• Other Authors: Chuang, Yung Jen
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/9uj33u

碩士 === 國立清華大學 === 生物資訊與結構生物研究所 === 103 === Myocardial infarction (MI) occurs when cardiac circulation is disrupted by coagulation, and the affected myocardium was damaged due to insufficient supply of blood. Failure to repair and regenerate damaged cardiac tissues after MI is a major cause of heart failure in human. In contrast, zebrafish heart has an extraordinary regenerative capacity. During zebrafish heart regeneration, the epicardium is activated and undergoes epithelial-to-mesenchymal transition (EMT) to generate epicardium-derived cells (EPDCs). EPDCs then migrate into the injured area where they generate various cell types to replace the damaged tissues. From our previous studies, it has been demonstrated that inflammation response is critical for triggering the regeneration process in zebrafish heart post injury. However, how the inflammation acts to activate the subsequent regenerative event, namely EMT of epicardium, is still unclear. To gain insight on this question, we targeted the COX-2/PGE2 pathway and aimed to verify whether PGE2 is the key mediator to connect inflammation with EMT during heart regeneration. For this study, we adapted an in vitro cell-based model of zebrafish epicardial cells to accompany in vivo assay as the research system. The epicardial primary cells had an epithelium-like morphology and markedly expressed the cell surface marker tight junction protein 1 (ZO-1). After PGE2 treatment, epicardial cells changed into a spindle-shaped morphology and lost the expression of ZO-1, which is consistent with the known characters of EMT. Interestingly, the expression of ZO-1 was partial restored when we treated the cells with a chemical TGF-β inhibitor SB-431542 (iALK5), which was further verified in vivo. In summary, we concluded that PGE2 is an epithelial-mesenchymal-transition mediator, whose function is mediated through the induction of TGF-β signaling pathway during zebrafish heart regeneration.