Vitamin D Stimulates Cardiomyocyte Proliferation and Controls Organ Size and Regeneration in Zebrafish.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Han, Y; Chen, A; Umansky, K-B; Oonk, KA; Choi, W-Y; Dickson, AL; Ou, J; Cigliola, V; Yifa, O; Cao, J; Tornini, VA; Cox, BD; Tzahor, E; Poss, KD

Published Date

  • March 25, 2019

Published In

Volume / Issue

  • 48 / 6

Start / End Page

  • 853 - 863.e5

PubMed ID

  • 30713073

Pubmed Central ID

  • 30713073

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2019.01.001

Language

  • eng

Conference Location

  • United States