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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

TitleNovel 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
Authors
KeywordsIGF-I
glucagon
HNF1α
CREB
signal transduction
Issue Date2019
PublisherFrontiers 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?
AbstractGlucagon, 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 Identifierhttp://hdl.handle.net/10722/277893
ISSN
2017 Impact Factor: 3.519
2015 SCImago Journal Rankings: 1.824

 

DC FieldValueLanguage
dc.contributor.authorBai, J-
dc.contributor.authorJiang, X-
dc.contributor.authorHe, M-
dc.contributor.authorChan, BCB-
dc.contributor.authorWong, AOL-
dc.date.accessioned2019-10-04T08:03:26Z-
dc.date.available2019-10-04T08:03:26Z-
dc.date.issued2019-
dc.identifier.citationFrontiers in Endocrinology, 2019, v. 10, p. article no. 605-
dc.identifier.issn1664-2392-
dc.identifier.urihttp://hdl.handle.net/10722/277893-
dc.description.abstractGlucagon, 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.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/endocrinology/-
dc.relation.ispartofFrontiers in Endocrinology-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectIGF-I-
dc.subjectglucagon-
dc.subjectHNF1α-
dc.subjectCREB-
dc.subjectsignal transduction-
dc.titleNovel 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.typeArticle-
dc.identifier.emailJiang, X: xue0129@hku.hk-
dc.identifier.emailHe, M: hemu@hkucc.hku.hk-
dc.identifier.emailChan, BCB: chancb@hku.hk-
dc.identifier.emailWong, AOL: olwong@hku.hk-
dc.identifier.authorityChan, BCB=rp02140-
dc.identifier.authorityWong, AOL=rp00806-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fendo.2019.00605-
dc.identifier.scopuseid_2-s2.0-85072830834-
dc.identifier.hkuros306423-
dc.identifier.volume10-
dc.identifier.spagearticle no. 605-
dc.identifier.epagearticle no. 605-
dc.publisher.placeSwitzerland-

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