Faculty Collaboration Database

Twist1 signaling in age-dependent decline in angiogenesis and lung regeneration. Aging (Albany NY) 2021 Mar 25;13(6):7781-7799

Date

03/26/2021

Pubmed ID

33764901

Pubmed Central ID

PMC8034921

DOI

10.18632/aging.202875

Scopus ID

2-s2.0-85103711251 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

Angiogenesis - the formation of new blood capillaries- is impaired in aging animals and contributes to the pathogenesis of age-related diseases. A transcription factor, Twist1, contributes to the pathogenesis of age- and angiogenesis-related diseases such as pulmonary fibrosis and atherosclerosis. However, the mechanism by which Twist1 controls age-dependent decline in angiogenesis remains unclear. In this report, we have demonstrated that the levels of Twist1 are higher, while the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) that stimulates angiogenesis, is lower in endothelial cells (ECs) isolated from aged human adipose tissues and mouse lungs compared to those from young tissues. Knockdown of Twist1 in aged human ECs increases the levels of PGC1α and angiogenic factor receptor, vascular endothelial growth factor receptor (VEGFR2), and restores EC proliferation and migration, while inhibition of PGC1α suppresses these effects. Knockdown of Twist1 in supplemented aged ECs also restores vascular networks in the subcutaneously implanted gel, while these effects are abrogated by knockdown of PGC1α. Age-dependent inhibition of post-pneumonectomy (PNX) lung growth is suppressed in Tie2-specific Twist1 conditional knockout mouse lungs, in which VEGFR2 expression increases after PNX. These results suggest that upregulation of endothelial Twist1 mediates age-dependent decline in angiogenesis and regenerative lung growth.

Author List

Hendee K, Hunyenyiwa T, Matus K, Toledo M, Mammoto A, Mammoto T

Authors

Kathryn Hendee in the CTSI department at Medical College of Wisconsin - CTSI
Akiko 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

Adult
Age Factors
Aged
Aging
Animals
Cell Movement
Cell Proliferation
Female
Humans
Lung
Male
Mice
Mice, Transgenic
Middle Aged
Neovascularization, Physiologic
Receptor, TIE-2
Regeneration
Signal Transduction
Twist-Related Protein 1
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2