Publicação
Deciphering the role of vitamin D in early lung development
| Resumo: | The high prevalence of vitamin D deficiency is currently considered a public health concern, affecting people of all ages worldwide, particularly childbearing women and children. There is now a large body of evidence linking maternal vitamin D deficiency and several maternal and fetal adverse health outcomes. Regarding the developing lung, it has been demonstrated that Vitamin D is crucial for lung maturation processes, and it influences the respiratory health of the offspring. Most observations point to a critical role of vitamin D during the later stages of lung development; however, little is known about its role in early branching stages, and nothing is known about its role in avian lung development. In this sense, this project aims to unravel the role of Vitamin D during early lung development, using the chicken embryo as a model. The present work unveils, for the first time, the expression pattern of Vitamin D signaling members (rxr-α, rxr-y, vdr, cyp24a1, and pdia3) by in situ hybridization in embryonic chick lung. The similarity between the expression patterns and low expression levels of these genes with the mammalian lung point to a similar and, eventually, minor role during these early stages of development. Furthermore, in an attempt to unveil the role of Vitamin D in chick lung branching, in vitro lung explants were performed. Supplementation studies revealed that Vitamin D supplementation significantly reduced lung size and branching, independently of the dose. Additionally, cyp24a1 increased expression in Vitamin D-treated explants, the main regulatory component of the pathway, confirmed Vitamin D signaling activation. Moreover, given the well-documented antiproliferative effect of vitamin D, we hypothesized that the significant reduction in lung size and branching could be explained by this event. EdU proliferation assay confirmed the presence of high proliferation levels in sites of active branching, distal and proximal lung, but further analysis demonstrated a significant reduction in proliferation levels in all Vitamin D-treated explants. This study unveils, for the first time, the potential role of vitamin D signaling in the early stages of chick pulmonary branching and contributes to better understand the intricate molecular events that ultimately regulate this complex process. Our results highlight the importance of regulating vitamin D levels during normal lung development and reinforce the need to establish appropriate doses and intervention windows to ensure an appropriate physiological response during embryonic development. |
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| Autores principais: | Caldeira, Inês Isabel Neves |
| Assunto: | Branching morphogenesis Chicken embryo Chick lung Pulmonary development Vitamin D Desenvolvimento pulmonar Embrião de galinha Pulmão de galinha Ramificação pulmonar Vitamina D |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | The high prevalence of vitamin D deficiency is currently considered a public health concern, affecting people of all ages worldwide, particularly childbearing women and children. There is now a large body of evidence linking maternal vitamin D deficiency and several maternal and fetal adverse health outcomes. Regarding the developing lung, it has been demonstrated that Vitamin D is crucial for lung maturation processes, and it influences the respiratory health of the offspring. Most observations point to a critical role of vitamin D during the later stages of lung development; however, little is known about its role in early branching stages, and nothing is known about its role in avian lung development. In this sense, this project aims to unravel the role of Vitamin D during early lung development, using the chicken embryo as a model. The present work unveils, for the first time, the expression pattern of Vitamin D signaling members (rxr-α, rxr-y, vdr, cyp24a1, and pdia3) by in situ hybridization in embryonic chick lung. The similarity between the expression patterns and low expression levels of these genes with the mammalian lung point to a similar and, eventually, minor role during these early stages of development. Furthermore, in an attempt to unveil the role of Vitamin D in chick lung branching, in vitro lung explants were performed. Supplementation studies revealed that Vitamin D supplementation significantly reduced lung size and branching, independently of the dose. Additionally, cyp24a1 increased expression in Vitamin D-treated explants, the main regulatory component of the pathway, confirmed Vitamin D signaling activation. Moreover, given the well-documented antiproliferative effect of vitamin D, we hypothesized that the significant reduction in lung size and branching could be explained by this event. EdU proliferation assay confirmed the presence of high proliferation levels in sites of active branching, distal and proximal lung, but further analysis demonstrated a significant reduction in proliferation levels in all Vitamin D-treated explants. This study unveils, for the first time, the potential role of vitamin D signaling in the early stages of chick pulmonary branching and contributes to better understand the intricate molecular events that ultimately regulate this complex process. Our results highlight the importance of regulating vitamin D levels during normal lung development and reinforce the need to establish appropriate doses and intervention windows to ensure an appropriate physiological response during embryonic development. |
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