| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Ingber, Donald E. Kalish, Brian T. Jenkins, Roger L. Inceoglu, Bora Butterfield, Catherine E. Kieran, Mark W. Simpson, Mary A. Lee, Craig R. Manthati, Vijaya L. Tomer, Kenneth B. Kaipainen, Arja Lih, Fred B. Bielenberg, Diane R. D'amore, Patricia A. Panigrahy, Dipak Yang, Jun Mammoto, Tadanori Le, Hau D. Huang, Sui Mudge, Dayna K. Falck, John R. Zeldin, Darryl C. Puder, Mark Edin, Matthew L. Akino, Tomoshige Mammoto, Akiko Benny, Ofra Hammock, Bruce D. |
| Description |
Author Affiliation: Panigrahy D ( Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. dpanigra@bidmc.harvard.edu); |
| Abstract |
Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
33 |
| Volume Number |
110 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2013-08-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Eicosanoids Pharmacology Endothelial Cells Metabolism Epoxy Compounds Neovascularization, Physiologic Physiology Regeneration Animals Chromatography, Liquid Epoxide Hydrolases Antagonists & Inhibitors Eye Blood Supply Immunohistochemistry Kidney Liver Lung Mice Mice, Transgenic Drug Effects Receptor, TIE-2 Genetics Tandem Mass Spectrometry Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
