LRP5 in age-related changes in vascular and alveolar morphogenesis in the lung. Aging (Albany NY) 2019 Jan 05;11(1):89-103
Date
01/07/2019Pubmed ID
30612120Pubmed Central ID
PMC6339783DOI
10.18632/aging.101722Scopus ID
2-s2.0-85060053785 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Aging is associated with impaired angiogenesis and lung alveolar regeneration, which contributes to the increased susceptibility to chronic lung diseases (CLD). We have reported that the Wnt ligand co-receptor, low-density lipoprotein receptor-related protein 5 (LRP5), stimulates angiogenesis and lung alveolar regeneration. However, the role of LRP5 in age-related decline in vascular and alveolar morphogenesis remains unclear. In this report, we have demonstrated that vascular and alveolar structures are disrupted in the 24-month (24M) old mouse lungs. The expression of LRP5 and the major angiogenic factors, VEGFR2 and Tie2, is lower in endothelial cells (ECs) isolated from 24M old mouse lungs compared to those from 2M old mouse lungs. Vascular and alveolar formation is attenuated in the hydrogel implanted on the 24M old mouse lungs, while overexpression of LRP5, which restores angiogenic factor expression, reverses vascular and alveolar morphogenesis in the gel. Compensatory lung growth after unilateral pneumonectomy is inhibited in 24M old mice, which is reversed by overexpression of LRP5. These results suggest that LRP5 mediates age-related inhibition of angiogenesis and alveolar morphogenesis. Modulation of LRP5 may be a novel intervention to rejuvenate regenerative ability in aged lung and will lead to the development of efficient strategies for aging-associated CLD.
Author List
Mammoto A, Muyleart M, Mammoto TAuthors
Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinTadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AgingAnimals
Epithelial Cells
Gene Knockdown Techniques
Low Density Lipoprotein Receptor-Related Protein-5
Lung
Mice
Mice, Inbred C57BL
Neovascularization, Physiologic
Pneumonectomy
Tissue Culture Techniques