Jornal de Pesquisa e Desenvolvimento em Aquicultura

Abstrato

The Liver-Enriched Transcription Factors HNF-1α, HNF-3β, and C/ EBPβ Contribute to the Growth Hormone-Induced Transcription of the Progranulin a Gene in Zebrafish (Danio Rerio)

Yi-Pei Lin,Wen-Jen Chung,Jen-Leih Wu*,Shao-Yang Hu*

Progranulin (PGRN) is a secreted growth factor that has been implicated in diverse biological processes
including wound healing, embryo development, morphogenesis and disease. We previously showed that PGRN is induced along with IGF-1 in tilapia liver upon GH administration. In the present study, we demonstrate that the coinduction of PGRN and IGF-1 by GH administration is a common regulation in fish also presented in zebrafish. To understand the regulatory mechanism of GH-induced PGRN expression, the zebrafish PGRN promoter was isolated and analyzed. We found that a region from -2400 to -3000 within PGRN promoter is essential for GH-induced PGRN expression. A promoter competition assay showed that HNF-3 β, HNF-1 α and C/EBP β binding motifs within the -2400/-3000 region of PGRN promoter contributed to GH-induced PGRN expression. The individual or concomitant transfection of HNF-3 β, HNF-1 α and C/EBP β into HepG2 cells showed that the three transcriptional regulators all participate in GH-induced PGRN expression with independent activities. These results demonstrated that the liverenriched transcription factors HNF-3 β, HNF-1 α and C/EBP β are involved in GH-induced PGRN expression in liver. We expect that these results will be useful in understanding the regulatory relationship between PGRN and IGF-1 in response to GH regulation.