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Negative impact of hyperglycaemia on mouse alveolar development.

ABSTRACT: Diabetes mellitus in pregnancy has been known to affect the embryonic development of various systems, including cardiovascular and nervous systems. However, whether this disease could have a negative impact on embryonic respiratory system remains controversial. In this study, we demonstrated that pregestational diabetes mellitus (PGDM)-induced defects in lung development in mice are mainly characterized by the changes in the morphological structure of the lung. Immunostaining and Western blotting showed that proliferation increased and apoptosis decreased in PGDM. Hyperglycaemia caused pulmonary tissue fibrationas manifested by an increase in Masson staining and decorin expression in PGDM lungs, and the immunofluorescent pro-SPC+ type II pulmonary epithelial cell number was decreased. The alteration of pulmonary epithelial cell differentiation might be due to hyperglycaemia-activated Wnt signalling and suppressed GATA6 expression in PGDM mouse lung tissues and MLE-12 cells. The treatment of MLE-12 cells with high glucose in the presence/absence of XAV939 or su5402 further proved that hyperglycaemia suppressed the expression of GATA6 and pro-SPC by activating Wnt signalling and induced the expression of decorin, ?-SMA and TGF-? by activating Fgf signalling. Therefore, in this study, we revealed that hyperglycemia induced dysfunctional pulmonary cell apoptosis and proliferation, as well as pulmonary myofibroblast hyperplasia, which contributed to the formation of aberrant structure of alveolar walls. Furthermore, the hyperglycaemia also inhibited the differentiation of pulmonary epithelial cells through the canonical Wnt and Fgf signalling, and the alteration of Fgf and Wnt signalling activated TGF-?, which would promote the AECII EMT process.

SUBMITTER: He MY

PROVIDER: S-EPMC5815430 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Negative impact of hyperglycaemia on mouse alveolar development.

He Mei-Yao MY Wang Guang G Han Sha-Sha SS Li Ke K Jin Ya Y Liu Meng M Si Zhen-Peng ZP Wang Ju J Liu Guo-Sheng GS Yang Xuesong X

Cell cycle (Georgetown, Tex.) 20171221 1

Diabetes mellitus in pregnancy has been known to affect the embryonic development of various systems, including cardiovascular and nervous systems. However, whether this disease could have a negative impact on embryonic respiratory system remains controversial. In this study, we demonstrated that pregestational diabetes mellitus (PGDM)-induced defects in lung development in mice are mainly characterized by the changes in the morphological structure of the lung. Immunostaining and Western blottin ...[more]

PMID: 29143549

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Project description:Background:Although the mouse is widely used to model human lung development, function, and disease, our understanding of the molecular mechanisms involved in alveolarization of the peripheral lung is incomplete. Recently, the Molecular Atlas of Lung Development Program (LungMAP) was funded by the National Heart, Lung, and Blood Institute to develop an integrated open access database (known as BREATH) to characterize the molecular and cellular anatomy of the developing lung. To support this effort, we designed detailed anatomic and cellular ontologies describing alveolar formation and maturation in both mouse and human lung.Description:While the general anatomic organization of the lung is similar for these two species, there are significant variations in the lung's architectural organization, distribution of connective tissue, and cellular composition along the respiratory tract. Anatomic ontologies for both species were constructed as partonomic hierarchies and organized along the lung's proximal-distal axis into respiratory, vascular, neural, and immunologic components. Terms for developmental and adult lung structures, tissues, and cells were included, providing comprehensive ontologies for application at varying levels of resolution. Using established scientific resources, multiple rounds of comparison were performed to identify common, analogous, and unique terms that describe the lungs of these two species. Existing biological and biomedical ontologies were examined and cross-referenced to facilitate integration at a later time, while additional terms were drawn from the scientific literature as needed. This comparative approach eliminated redundancy and inconsistent terminology, enabling us to differentiate true anatomic variations between mouse and human lungs. As a result, approximately 300 terms for fetal and postnatal lung structures, tissues, and cells were identified for each species.Conclusion:These ontologies standardize and expand current terminology for fetal and adult lungs, providing a qualitative framework for data annotation, retrieval, and integration across a wide variety of datasets in the BREATH database. To our knowledge, these are the first ontologies designed to include terminology specific for developmental structures in the lung, as well as to compare common anatomic features and variations between mouse and human lungs. These ontologies provide a unique resource for the LungMAP, as well as for the broader scientific community.

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Negative impact of hyperglycaemia on mouse alveolar development.

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Negative impact of hyperglycaemia on mouse alveolar development.

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