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. 2022 Jul 26;23(15):8244.
doi: 10.3390/ijms23158244.

Transcriptome Profile of Thyroid Glands in Bile Duct Ligation Mouse Model

Danbi Jo  1   2 , Hee Kyung Kim  3 , Young-Kook Kim  4 , Juhyun Song  1   2
Affiliations

Transcriptome Profile of Thyroid Glands in Bile Duct Ligation Mouse Model

Danbi Jo et al. Int J Mol Sci. .

Abstract

Thyroid hormone (TH) contributes to multiple cellular mechanisms in the liver, muscle cells, adipose tissue, and brain, etc. In particular, the liver is an important organ in TH metabolism for the conversion of thyronine (T4) into triiodothyronine (T3) by the deiodinase enzyme. TH levels were significantly decreased and thyroid-stimulating hormone (TSH) levels were significantly increased in patients with liver failure compared with normal subjects. Among liver failure diseases, hepatic encephalopathy (HE) deserves more attention because liver damage and neuropathologies occur simultaneously. Although there is numerous evidence of TH dysregulation in the HE model, specific mechanisms and genetic features of the thyroid glands in the HE model are not fully understood. Here, we investigated the significantly different genes in the thyroid glands of a bile duct ligation (BDL) mouse model as the HE model, compared to the thyroid glands of the control mouse using RNA sequencing. We also confirmed the alteration in mRNA levels of thyroid gland function-related genes in the BDL mouse model. Furthermore, we evaluated the increased level of free T4 and TSH in the BDL mouse blood. Thus, we emphasize the potential roles of TH in liver metabolism and suggest that thyroid dysfunction-related genes in the HE model should be highlighted for finding the appropriate solution for an impaired thyroid system in HE.

Keywords: RNA sequencing; bile duct ligation (BDL) model; hepatic encephalopathy (HE); thyroid gland; thyroid hormone (TH).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Analysis of transcriptomic data from the thyroid gland tissue of BDL mouse models. (A) Process for analysis of the transcriptome data. (B) Volcano plots of the BDL mouse model. The X-axis showed the log2-transformed fold change in each group and the Y-axis represents the −log10(p-value) value. Red dots indicate the genes with a significantly changed expression.
Figure 2
Figure 2
Selected genes with significant expression change in the thyroid gland tissue of BDL mouse models. (A,B) The common genes with a significant expression change in the thyroid gland tissue in BDL models. The graphs depict (A) the top 15 genes with increased expression and (B) the top 15 genes with decreased expression.
Figure 3
Figure 3
Functional analysis of genes with increased expression in BDL mouse groups. (A) KEGG pathway analysis for genes with increased expression in the BDL mouse group. The significantly changed pathways based on the false discovery rate (FDR) q-value are shown. (B) GO analysis for genes with increased expression in the BDL mouse group. The top 20 GO terms based on the FDR q-value are shown.
Figure 4
Figure 4
Transcriptional analysis of the common genes in the BDL mouse group. (A) BART prediction and ChAE3 prediction transcription factor analysis. (B) Heatmap of well grouping between the groups. (C,D) Signal networking data.
Figure 5
Figure 5
ELISA data. (A) ELISA to detect free T4, (B) T3, and (C) TSH in blood serum of sham and BDL mice. p-value *** is <0.001 and n.s means no significant.
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