Thyroid hormone deprival and TSH/TSHR signaling deficiency lead to central hypothyroidism-associated intestinal dysplasia
Copyright © 2024 Elsevier Inc. All rights reserved..
BACKGROUND: Central hypothyroidism (CH) is characterized by low T4 levels and reduced levels or bioactivity of circulating TSH. However, there is a lack of studies on CH-related intestinal maldevelopment. In particular, the roles of TH and TSH/TSHR signaling in CH-related intestinal maldevelopment are poorly understood. Herein, we utilized Tshr-/- mice as a congenital hypothyroidism model with TH deprival and absence of TSHR signaling.
METHODS: The morphological characteristics of intestines were determined by HE staining, periodic acid-shiff staining, and immunohistochemical staining. T4 was administrated into the offspring of homozygous mice from the fourth postnatal day through weaning or administrated after weaning. RT-PCR was used to evaluate the expression of markers of goblet cells and intestinal digestive enzymes. Single-cell RNA-sequencing analysis was used to explore the cell types and gene profiles of metabolic alternations in early-T4-injected Tshr-/- mice.
KEY FINDINGS: Tshr deletion caused significant growth retardation and intestinal maldevelopment, manifested as smaller and more slender small intestines due to reduced numbers of stem cells and differentiated epithelial cells. Thyroxin supplementation from the fourth postnatal day, but not from weaning, significantly rescued the abnormal intestinal structure and restored the decreased number of proliferating intestinal cells in crypts of Tshr-/- mice. Tshr-/- mice with early-life T4 injections had more early goblet cells and impaired metabolism compared to Tshr+/+ mice.
SIGNIFICANCE: TH deprival leads to major defects of CH-associated intestinal dysplasia while TSH/TSHR signaling deficiency promotes the differentiation of goblet cells and impairs nutrition metabolism.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:345 |
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| Enthalten in: |
Life sciences - 345(2024) vom: 15. Apr., Seite 122577 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Peng, Li [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.04.2024 Date Revised 27.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.lfs.2024.122577 |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Peng, Li |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Thyroid hormone deprival and TSH/TSHR signaling deficiency lead to central hypothyroidism-associated intestinal dysplasia |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Central hypothyroidism (CH) is characterized by low T4 levels and reduced levels or bioactivity of circulating TSH. However, there is a lack of studies on CH-related intestinal maldevelopment. In particular, the roles of TH and TSH/TSHR signaling in CH-related intestinal maldevelopment are poorly understood. Herein, we utilized Tshr-/- mice as a congenital hypothyroidism model with TH deprival and absence of TSHR signaling | ||
| 520 | |a METHODS: The morphological characteristics of intestines were determined by HE staining, periodic acid-shiff staining, and immunohistochemical staining. T4 was administrated into the offspring of homozygous mice from the fourth postnatal day through weaning or administrated after weaning. RT-PCR was used to evaluate the expression of markers of goblet cells and intestinal digestive enzymes. Single-cell RNA-sequencing analysis was used to explore the cell types and gene profiles of metabolic alternations in early-T4-injected Tshr-/- mice | ||
| 520 | |a KEY FINDINGS: Tshr deletion caused significant growth retardation and intestinal maldevelopment, manifested as smaller and more slender small intestines due to reduced numbers of stem cells and differentiated epithelial cells. Thyroxin supplementation from the fourth postnatal day, but not from weaning, significantly rescued the abnormal intestinal structure and restored the decreased number of proliferating intestinal cells in crypts of Tshr-/- mice. Tshr-/- mice with early-life T4 injections had more early goblet cells and impaired metabolism compared to Tshr+/+ mice | ||
| 520 | |a SIGNIFICANCE: TH deprival leads to major defects of CH-associated intestinal dysplasia while TSH/TSHR signaling deficiency promotes the differentiation of goblet cells and impairs nutrition metabolism | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Congenital hypothyroidism | |
| 650 | 4 | |a Intestinal adult stem cell | |
| 650 | 4 | |a Intestinal dysplasia | |
| 650 | 4 | |a Thyroid hormone deprival | |
| 650 | 4 | |a Thyrotropin receptor | |
| 650 | 7 | |a Receptors, G-Protein-Coupled |2 NLM | |
| 650 | 7 | |a Receptors, Thyrotropin |2 NLM | |
| 650 | 7 | |a Thyroid Hormones |2 NLM | |
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| 700 | 1 | |a Luan, Sisi |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhan, Huidong |e verfasserin |4 aut | |
| 700 | 1 | |a Ge, Yueping |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Yixiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Shanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Haiqing |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jiajun |e verfasserin |4 aut | |
| 700 | 1 | |a He, Zhao |e verfasserin |4 aut | |
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