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Acceleration of Lung Regeneration by Platelet-Rich Plasma Extract through the Low-Density Lipoprotein Receptor-Related Protein 5-Tie2 Pathway. Am J Respir Cell Mol Biol 2016 Jan;54(1):103-13

Date

06/20/2015

Pubmed ID

26091161

Pubmed Central ID

PMC5455682

DOI

10.1165/rcmb.2015-0045OC

Scopus ID

2-s2.0-85047289720 (requires institutional sign-in at Scopus site)   33 Citations

Abstract

Angiogenesis, the growth of new blood vessels, plays a key role in organ development, homeostasis, and regeneration. The cooperation of multiple angiogenic factors, rather than a single factor, is required for physiological angiogenesis. Recently, we have reported that soluble platelet-rich plasma (PRP) extract, which contains abundant angiopoietin-1 and multiple other angiogenic factors, stimulates angiogenesis and maintains vascular integrity in vitro and in vivo. In this report, we have demonstrated that mouse PRP extract increases phosphorylation levels of the Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) and thereby activates angiogenic factor receptor Tie2 in endothelial cells (ECs) and accelerates EC sprouting and lung epithelial cell budding in vitro. PRP extract also increases phosphorylation levels of Tie2 in the mouse lungs and accelerates compensatory lung growth and recovery of exercise capacity after unilateral pneumonectomy in mice, whereas soluble Tie2 receptor or Lrp5 knockdown attenuates the effects of PRP extract. Because human PRP extract is generated from autologous peripheral blood and can be stored at -80°C, our findings may lead to the development of novel therapeutic interventions for various angiogenesis-related lung diseases and to the improvement of strategies for lung regeneration.

Author List

Mammoto T, Chen Z, Jiang A, Jiang E, Ingber DE, Mammoto A

Authors

Akiko Mammoto MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin
Tadanori Mammoto PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Line
Cell Proliferation
Coculture Techniques
Epithelial Cells
Exercise Tolerance
Human Umbilical Vein Endothelial Cells
Humans
Low Density Lipoprotein Receptor-Related Protein-5
Lung
Mice, Inbred C57BL
Mice, Knockout
Neovascularization, Physiologic
Phosphorylation
Platelet-Rich Plasma
Pneumonectomy
RNA Interference
Receptor, TIE-2
Recovery of Function
Regeneration
Signal Transduction
Time Factors
Transfection