Rigolet M et al. (2022), Crosstalk between Thyroid Hormone and Corticost...

XB-ART-59478

Int J Mol Sci 2022 Nov 08;2322:. doi: 10.3390/ijms232213715.

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Crosstalk between Thyroid Hormone and Corticosteroid Signaling Targets Cell Proliferation in Xenopus tropicalis Tadpole Liver.

Rigolet M , Buisine N , Scharwatt M , Duvernois-Berthet E , Buchholz DR , Sachs LM .

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Thyroid hormones (TH) and glucocorticoids (GC) are involved in numerous developmental and physiological processes. The effects of individual hormones are well documented, but little is known about the joint actions of the two hormones. To decipher the crosstalk between these two hormonal pathways, we conducted a transcriptional analysis of genes regulated by TH, GC, or both hormones together in liver of Xenopus tropicalis tadpoles using RNA-Seq. Among the differentially expressed genes (DE), 70.5% were regulated by TH only, 0.87% by GC only, and 15% by crosstalk between the two hormones. Gene ontology analysis of the crosstalk-regulated genes identified terms referring to DNA replication, DNA repair, and cell-cycle regulation. Biological network analysis identified groups of genes targeted by the hormonal crosstalk and corroborated the gene ontology analysis. Specifically, we found two groups of functionally linked genes (chains) mainly composed of crosstalk-regulated hubs (highly interactive genes), and a large subnetwork centred around the crosstalk-regulated genes psmb6 and cdc7. Most of the genes in the chains are involved in cell-cycle regulation, as are psmb6 and cdc7, which regulate the G2/M transition. Thus, the biological action of these two hormonal pathways acting together in the liver targets cell-cycle regulation.

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Species referenced: Xenopus tropicalis
Genes referenced: cdc7 psmb6
GO keywords: liver development [+]

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References [+] :

Andersen, Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. 2004, Pubmed

	Graphical Abstract.
	Figure 1. T3 and CORT treatments induce major changes in gene expression: (A) MA-plots for DE genes following each treatment; (B) validation of the RNA-Seq data by RT-qPCR carried out for 21 genes selected with an average expression level above 100 reads; (C) RT-qPCR validation of gene expression following T3, CORT, and T3 + CORT treatments (statistical significance according to Mann–Whitney test with * p < 0.05; p < 0.01; * p < 0.001); (D) gene ontology analysis of the DE genes.
	Figure 2. Expression profile-based clustering of the DE genes reveals crosstalk between T3 and CORT signaling. The first three letters describe the expression changes compared to the control. The fourth letter illustrates the type of crosstalk response: “N” for no crosstalk, “P” for potentiated, “A” for mutually antagonized, “a” for singly antagonized, and “s” or “S” for synergistic. With “s”, gene expression can be also regulated with each hormone individually, whereas, with “S”, gene regulation is strictly dependent on the action of both hormones simultaneously.
	Figure 3. Gene ontology analysis highlights the different biological processes regulated by T3 and CORT and the crosstalk between the two hormones.
	Figure 4. Network analysis of gene expression changes: (A) network for T3 and CORT DE genes (blue), crosstalk-regulated genes (red), and non-DE genes (grey). (B) Characteristics of the network. (C) Heatmap showing the expression pattern and the connections of the hubs. (D) Chains. (E) Gene ontology analysis of the crosstalk-regulated hubs compared to the network. (F) psmb6-cdc7 subnetwork. (G) Validation of the crosstalk regulation of psmb6 and cdc7 by RT-qPCR. * p < 0.05 and >0.01.
	Figure S1. Decision tree highliting the effects of the hormonal treatments. n stands for No and y for Yes, t is for threshold
	Figure S1. Decision tree highliting the effects of the hormonal treatments. n stands for No and y for Yes, t is for threshold