Progranulin A-mediated MET Signaling is Essential for Liver Morphogenesis in Zebrafish

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Oct 22

PMID 20961855

Citations 19

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Progranulin A Promotes Compensatory Hepatocyte Proliferation via HGF/c-Met Signaling after Partial Hepatectomy in Zebrafish.

Chiang K, Li Y, Li Y, Huang S, Wu C, Gong H Int J Mol Sci. 2021; 22(20).

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A zebrafish model of granulin deficiency reveals essential roles in myeloid cell differentiation.

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Modeling Lysosomal Storage Diseases in the Zebrafish.

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