PUBLICATION
Thyroid hormones regulate goblet cell differentiation and Fgf19-Fgfr4 signaling
- Authors
- Blitz, E., Matsuda, H., Guenther, S., Morikawa, T., Kubota, Y., Zada, D., Lerer-Goldshtein, T., Stainier, D.Y.R., Appelbaum, L.
- ID
- ZDB-PUB-210307-32
- Date
- 2021
- Source
- Endocrinology 162(5): (Journal)
- Registered Authors
- Appelbaum, Lior, Blitz, Einat, Matsuda, Hiroki, Stainier, Didier
- Keywords
- intestine, thyroid, zebrafish
- MeSH Terms
-
- Animals
- Cell Proliferation
- Disease Models, Animal
- Fibroblast Growth Factors/genetics
- Fibroblast Growth Factors/metabolism*
- Goblet Cells/cytology
- Goblet Cells/metabolism*
- Humans
- Hypothyroidism/genetics
- Hypothyroidism/metabolism*
- Hypothyroidism/physiopathology
- Intestinal Mucosa/growth & development
- Intestinal Mucosa/metabolism
- Receptor, Fibroblast Growth Factor, Type 4/genetics
- Receptor, Fibroblast Growth Factor, Type 4/metabolism*
- Signal Transduction
- Thyroxine/metabolism*
- Triiodothyronine/metabolism*
- Zebrafish/genetics
- Zebrafish/growth & development
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 33675223 Full text @ Endocrinology
Citation
Blitz, E., Matsuda, H., Guenther, S., Morikawa, T., Kubota, Y., Zada, D., Lerer-Goldshtein, T., Stainier, D.Y.R., Appelbaum, L. (2021) Thyroid hormones regulate goblet cell differentiation and Fgf19-Fgfr4 signaling. Endocrinology. 162(5):.
Abstract
Hypothyroidism is a common pathological condition that is characterized by insufficient activity of the thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), in the whole body or in specific tissues. Hypothyroidism is associated with inadequate development of the intestine as well as gastrointestinal diseases. We utilized a zebrafish model of hypothyroidism in order to identify and characterize TH-modulated genes and cellular pathways controlling intestine development. In the intestine of hypothyroid juveniles and adults, the number of mucus-secreting goblet cells was reduced, and this phenotype could be rescued by T3 treatment. Transcriptome profiling revealed dozens of differentially expressed genes in the intestine of hypothyroid adults compared to controls. Notably, the expression of genes encoding to Fgf19 and its receptor Fgfr4 was markedly increased in the intestine of hypothyroid adults, and treatment with T3 normalized it. Blocking FGF signaling, using an inducible dominant negative Fgfr transgenic line, rescued the number of goblet cells in hypothyroid adults. These results show that THs inhibit the Fgf19-Fgfr4 signaling pathway, which is associated with inhibition of goblet cell differentiation in hypothyroidism. Both the TH and Fgf19-Fgfr4 signaling pathways can be pharmaceutical targets for the treatment of TH-related gastrointestinal diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping