Dataset Information

Novel Mechanisms for IGF-I Regulation by Glucagon in Carp Hepatocytes: Up-Regulation of HNF1? and CREB Expression via Signaling Crosstalk for IGF-I Gene Transcription.

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 HNF1?, 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, HNF1?, and CREB mRNA levels, induce CREB phosphorylation, and up-regulate HNF1? and CREB protein expression. The effects on IGF-I, HNF1?, 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 HNF1? 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 ?T3 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 HNF1? 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 HNF1? 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.

SUBMITTER: Bai J

PROVIDER: S-EPMC6734168 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

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.

Bai Jin J Jiang Xue X He Mulan M Chan Ben C B BCB Wong Anderson O L AOL

Frontiers in endocrinology 20190903

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 cl ...[more]

PMID: 31551932

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Project description:Purpose:Salinity is an important environmental factor that affects the physiological activities of fish. The goals of this study are investigating the effect of different saline-alkali stress on grass carp (Ctenopharyngodon idella). Methods: Grass carp individuals, averaging 12 cm in body length, were obtained from Duofu fish farm (Wuhan, China) and cultured at recirculating aquaculture system for 2 weeks before the experiment began. For the challenge, all grass carp were randomly divided into three groups, and then cultured at saline-alkali water with the concentration of 0, 3‰ and 6‰. After 30 days, some grass crap cultured at 3‰ and 6‰ saline-alkali water were injured. At the same time, gill samples of grass carp were collected from 0, 3‰ (grass carp was not injured), 3‰ (grass carp was injured), 6‰ (grass carp was not injured) and 6‰ (grass carp was injured)saline-alkali groups. Total RNA of all samples was isolated using TRIzol® Reagent (Invitrogen) according to the manufacturer's introduction. RNA integrity was assessed using an Agilent 2100 bioanalyzer (Agilent, USA). Samples with RNA integrity numbers (RINs) ≥ 7.5 were subjected to cDNA library construction using TruseqTM RNA sample prep Kit (Illumina). Results:A total of 15 were processed for transcriptome sequencing, generating 94.99Gb Clean Data. At least 5.76Gb clean data were generated for each sample with minimum 91.87% of clean data achieved quality score of Q30. Clean reads of each sample were mapped to specified reference genome. Mapping ratio ranged from 88.59% to 92.84%. The expression of genes was quantified and differentially expressed genes were identified based on their expression.Criteria for differentially expressed genes was set as Fold Change(FC)≥1.5 and Pvalue<0.05. Fold change(FC) refers to the ratio of gene expression in two samples. These DEGs were further processed for functional annotation and enrichment analysis. Conclusions: Our study represents Effects and molecular regulation mechanisms of saline-alkali stress on the healthy grass carp by using RNA-seqtechnology. Our results show that saline-alkali stress will impair the immune system of grass carp.

Dataset Information

Novel Mechanisms for IGF-I Regulation by Glucagon in Carp Hepatocytes: Up-Regulation of HNF1? and CREB Expression via Signaling Crosstalk for IGF-I Gene Transcription.

Publications

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.

Similar Datasets

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