Vascular endothelium plays a key role in directing pulmonary epithelial cell differentiation
Copyright policy )Vascular endothelium plays a key role in directing pulmonary epithelial cell differentiation
The vascular endothelium is critical for induction of appropriate lineage differentiation in organogenesis. In this study, we report that dysfunctional pulmonary endothelium, resulting from the loss of matrix Gla protein (MGP), causes ectopic hepatic differentiation in the pulmonary epithelium. We demonstrate uncontrolled induction of the hepatic growth factor (HGF) caused by dysregulated cross talk between pulmonary endothelium and epithelium in Mgp-null lungs. Elevated HGF induced hepatocyte nuclear factor 4 α (Hnf4a), which competed with NK2 homeobox 1 (Nkx2.1) for binding to forkhead box A2 (Foxa2) to drive hepatic differentiation in Mgp-null airway progenitor cells. Limiting endothelial HGF reduced Hnf4a, abolished interference of Hnf4a with Foxa2, and reduced hepatic differentiation in Mgp-null lungs. Together, our results suggest that endothelial–epithelial interactions, maintained by MGP, are essential in pulmonary cell differentiation.
- University of California System United States
- Howard Hughes Medical Institute United States
- University of California, Los Angeles United States
- University of California, San Francisco United States
- UCLA Health United States
Knockout, Cell Communication, Respiratory Mucosa, Medical and Health Sciences, Mice, Vascular, 2.1 Biological and endogenous factors, Animals, Endothelium, Aetiology, Lung, Research Articles, Mice, Knockout, Hepatocyte Growth Factor, Liver Disease, Proteins, Cell Differentiation, Epithelial Cells, Biological Sciences, Hepatocyte Nuclear Factor 4, Hepatocyte Nuclear Factor 3-beta, Endothelium, Vascular, Digestive Diseases, Developmental Biology
Knockout, Cell Communication, Respiratory Mucosa, Medical and Health Sciences, Mice, Vascular, 2.1 Biological and endogenous factors, Animals, Endothelium, Aetiology, Lung, Research Articles, Mice, Knockout, Hepatocyte Growth Factor, Liver Disease, Proteins, Cell Differentiation, Epithelial Cells, Biological Sciences, Hepatocyte Nuclear Factor 4, Hepatocyte Nuclear Factor 3-beta, Endothelium, Vascular, Digestive Diseases, Developmental Biology
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