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Article: Novel mechanisms for IGF-I regulation by glucagon in carp hepatocytes: Up-regulation of HNF1α and CREB expression via signaling crosstalk for IGF-I gene transcription
Title | Novel mechanisms for IGF-I regulation by glucagon in carp hepatocytes: Up-regulation of HNF1α and CREB expression via signaling crosstalk for IGF-I gene transcription |
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Authors | |
Keywords | IGF-I glucagon HNF1α CREB signal transduction |
Issue Date | 2019 |
Publisher | Frontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/endocrinology/ |
Citation | Frontiers in Endocrinology, 2019, v. 10, p. article no. 605 How to Cite? |
Abstract | Glucagon, a key hormone for glucose homeostasis, can exert functional crosstalk with somatotropic axis via modification of IGF-I expression. However, its effect on IGF-I regulation is highly variable in different studies and the mechanisms involved are largely unknown. Using grass carp as a model, the signal transduction and transcriptional mechanisms for IGF-I regulation by glucagon were examined in Cyprinid species. As a first step, the carp HNF1α, a liver-enriched transcription factor, was cloned and confirmed to be a single-copy gene expressed in the liver. In grass carp hepatocytes, glucagon treatment could elevate IGF-I, HNF1α, and CREB mRNA levels, induce CREB phosphorylation, and up-regulate HNF1α and CREB protein expression. The effects on IGF-I, HNF1α, and CREB gene expression were mediated by cAMP/PKA and PLC/IP3/PKC pathways with differential coupling with the MAPK and PI3K/Akt cascades. During the process, protein:protein interaction between HNF1α and CREB and recruitment of RNA Pol-II to IGF-I promoter also occurred with a rise in IGF-I primary transcript level. In parallel study to examine grass carp IGF-I promoter activity expressed in αT3 cells, similar pathways for post-receptor signaling were also confirmed in glucagon-induced IGF-I promoter activation and the trans-activating effect by glucagon was mediated by the binding sites for HNF1α and CREB located in the proximal region of IGF-I promoter. Our findings, as a whole, shed light on a previously undescribed mechanism for glucagon-induced IGF-I gene expression by increasing HNF1α and CREB production via functional crosstalk of post-receptor signaling. Probably, by protein:protein interaction between the two transcription factors and subsequent transactivation via their respective cis-acting elements in the IGF-I promoter, IGF-I gene transcription can be initiated by glucagon at the hepatic level. |
Persistent Identifier | http://hdl.handle.net/10722/277893 |
ISSN | 2023 Impact Factor: 3.9 2023 SCImago Journal Rankings: 1.240 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Bai, J | - |
dc.contributor.author | Jiang, X | - |
dc.contributor.author | He, M | - |
dc.contributor.author | Chan, BCB | - |
dc.contributor.author | Wong, AOL | - |
dc.date.accessioned | 2019-10-04T08:03:26Z | - |
dc.date.available | 2019-10-04T08:03:26Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Frontiers in Endocrinology, 2019, v. 10, p. article no. 605 | - |
dc.identifier.issn | 1664-2392 | - |
dc.identifier.uri | http://hdl.handle.net/10722/277893 | - |
dc.description.abstract | Glucagon, a key hormone for glucose homeostasis, can exert functional crosstalk with somatotropic axis via modification of IGF-I expression. However, its effect on IGF-I regulation is highly variable in different studies and the mechanisms involved are largely unknown. Using grass carp as a model, the signal transduction and transcriptional mechanisms for IGF-I regulation by glucagon were examined in Cyprinid species. As a first step, the carp HNF1α, a liver-enriched transcription factor, was cloned and confirmed to be a single-copy gene expressed in the liver. In grass carp hepatocytes, glucagon treatment could elevate IGF-I, HNF1α, and CREB mRNA levels, induce CREB phosphorylation, and up-regulate HNF1α and CREB protein expression. The effects on IGF-I, HNF1α, and CREB gene expression were mediated by cAMP/PKA and PLC/IP3/PKC pathways with differential coupling with the MAPK and PI3K/Akt cascades. During the process, protein:protein interaction between HNF1α and CREB and recruitment of RNA Pol-II to IGF-I promoter also occurred with a rise in IGF-I primary transcript level. In parallel study to examine grass carp IGF-I promoter activity expressed in αT3 cells, similar pathways for post-receptor signaling were also confirmed in glucagon-induced IGF-I promoter activation and the trans-activating effect by glucagon was mediated by the binding sites for HNF1α and CREB located in the proximal region of IGF-I promoter. Our findings, as a whole, shed light on a previously undescribed mechanism for glucagon-induced IGF-I gene expression by increasing HNF1α and CREB production via functional crosstalk of post-receptor signaling. Probably, by protein:protein interaction between the two transcription factors and subsequent transactivation via their respective cis-acting elements in the IGF-I promoter, IGF-I gene transcription can be initiated by glucagon at the hepatic level. | - |
dc.language | eng | - |
dc.publisher | Frontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/endocrinology/ | - |
dc.relation.ispartof | Frontiers in Endocrinology | - |
dc.rights | This Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | IGF-I | - |
dc.subject | glucagon | - |
dc.subject | HNF1α | - |
dc.subject | CREB | - |
dc.subject | signal transduction | - |
dc.title | Novel mechanisms for IGF-I regulation by glucagon in carp hepatocytes: Up-regulation of HNF1α and CREB expression via signaling crosstalk for IGF-I gene transcription | - |
dc.type | Article | - |
dc.identifier.email | Jiang, X: xue0129@hku.hk | - |
dc.identifier.email | He, M: hemu@hkucc.hku.hk | - |
dc.identifier.email | Chan, BCB: chancb@hku.hk | - |
dc.identifier.email | Wong, AOL: olwong@hku.hk | - |
dc.identifier.authority | Chan, BCB=rp02140 | - |
dc.identifier.authority | Wong, AOL=rp00806 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.3389/fendo.2019.00605 | - |
dc.identifier.scopus | eid_2-s2.0-85072830834 | - |
dc.identifier.hkuros | 306423 | - |
dc.identifier.volume | 10 | - |
dc.identifier.spage | article no. 605 | - |
dc.identifier.epage | article no. 605 | - |
dc.identifier.isi | WOS:000483520900001 | - |
dc.publisher.place | Switzerland | - |
dc.identifier.issnl | 1664-2392 | - |