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Title: Progranulin A-mediated MET signaling is essential for liver morphogenesis in zebrafish
Authors: Yen-Hsing Li;Mark Hung-Chih Chen;Hong-Yi Gong;Shao-Yang Hu;Ya-Wen Li;Gen-Hwa Lin;Ching-Chun Lin;Wangta Liu;Jen-Leih Wu
Contributors: 中研院中研院:細生所;弘光科技大學:生技系;國立臺灣海洋大學:水產養殖系;屏東科技大學:生科系
Keywords: development;liver;growth;zebrafish;progranulin
Date: 2010-12-24
Issue Date: 2012-05-02T07:59:56Z
Publisher: Journal of Biological Chemistry
Abstract: Abstract:The mechanism that regulates embryonic liver morphogenesis remains elusive. Progranulin (PGRN) is postulated to play a critical role in regulating pathological liver growth. Nevertheless, the exact regulatory mechanism of PGRN in relation to its functional role in embryonic liver development remains to be elucidated. In our study, the knockdown of progranulin A (GrnA), an orthologue of mammalian PGRN, using antisense morpholinos resulted in impaired liver morphogenesis in zebrafish (Danio rerio). The vital role of GrnA in hepatic outgrowth and not in liver bud formation was further confirmed using whole-mount in situ hybridization markers. In addition, a GrnA deficiency was also found to be associated with the deregulation of MET-related genes in the neonatal liver using a microarray analysis. In contrast, the decrease in liver size that was observed in grnA morphants was avoided when ectopic MET expression was produced by co-injecting met mRNA and grnA morpholinos. This phenomenon suggests that GrnA might play a role in liver growth regulation via MET signaling. Furthermore, our study has shown that GrnA positively modulates hepatic MET expression both in vivo and in vitro. Therefore, our data have indicated that GrnA plays a vital role in embryonic liver morphogenesis in zebrafish. As a result, a novel link between PGRN and MET signaling is proposed.
Relation: 285(52), pp.41001-41009
Appears in Collections:[Department of Aquaculture] Periodical Articles

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