Twist1 signaling in age-dependent decline in angiogenesis and lung regeneration

• DOI: 10.18632/aging.202875
• Publication Date: 2021-03-25T16:19:27Z
• Authors: Kathryn Hendee; Tendai Hunyenyiwa; Kienna Matus; Maria Toledo; Akiko Mammoto; Tadanori Mammoto
• Keywords: Adult; Male; Vascular Endothelial Growth Factor A; 0301 basic medicine; Aging; Twist-Related Protein 1; Age Factors; Neovascularization, Physiologic; Mice, Transgenic; Middle Aged; Receptor, TIE-2; Mice; 03 medical and health sciences; Cell Movement; Animals; Humans; Regeneration; Female; Lung; Research Paper; Aged; Cell Proliferation; Signal Transduction

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