Vitamin D Stimulates Cardiomyocyte Proliferation and Controls Organ Size and Regeneration in Zebrafish
| Autor: | Valerie A. Tornini, Ben D. Cox, Valentina Cigliola, Yanchao Han, Kfir-Baruch Umansky, Kenneth D. Poss, Jingli Cao, Jianhong Ou, Eldad Tzahor, Amy L. Dickson, Oren Yifa, Wen-Yee Choi, Kelsey A. Oonk, Anzhi Chen |
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| Rok vydání: | 2019 |
| Předmět: |
Cell type
Embryo Nonmammalian Calcitriol receptor General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Vitamin D and neurology Animals Regeneration Myocytes Cardiac Vitamin D Molecular Biology Zebrafish Cell Proliferation 030304 developmental biology 0303 health sciences biology Cell growth Regeneration (biology) Cell Cycle Alfacalcidol Heart Organ Size Cell Biology Zebrafish Proteins biology.organism_classification Embryonic stem cell Cell biology chemistry Organ Specificity Mitogens 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | Developmental Cell. 48:853-863.e5 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2019.01.001 |
| Popis: | Summary Attaining proper organ size during development and regeneration hinges on the activity of mitogenic factors. Here, we performed a large-scale chemical screen in embryonic zebrafish to identify cardiomyocyte mitogens. Although commonly considered anti-proliferative, vitamin D analogs like alfacalcidol had rapid, potent mitogenic effects on embryonic and adult cardiomyocytes in vivo. Moreover, pharmacologic or genetic manipulation of vitamin D signaling controlled proliferation in multiple adult cell types and dictated growth rates in embryonic and juvenile zebrafish. Tissue-specific modulation of vitamin D receptor (VDR) signaling had organ-restricted effects, with cardiac VDR activation causing cardiomegaly. Alfacalcidol enhanced the regenerative response of injured zebrafish hearts, whereas VDR blockade inhibited regeneration. Alfacalcidol activated cardiac expression of genes associated with ErbB2 signaling, while ErbB2 inhibition blunted its effects on cell proliferation. Our findings identify vitamin D as mitogenic for cardiomyocytes and other cell types in zebrafish and indicate a mechanism to regulate organ size and regeneration. |
| Databáze: | OpenAIRE |
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