Bruce D. Hammock, Ph.D.
University of California, Davis
NIEHS Grants P42ES004699, R01ES002710, R01ES013933
NIEHS-supported work found that endothelial-derived epoxyeicosatrienoic acids (EETs) are critical in accelerating in vivo tissue growth. The new findings could lead to new therapies for improving tissue repair and wound healing in the liver, lungs, and kidneys.
EETs are lipid mediators that regulate pain, inflammation, angiogenesis, and vascular tone. To better understand the role of these lipid mediators in tissue regeneration, the researchers used genetic and pharmacological tools to control endogenous EET levels in seven animal models: liver regeneration, kidney compensatory growth, lung compensatory growth, angiogenesis Matrigel plug assay, corneal micropocket assay, wound healing, and neonatal retinal vessel formation.
The investigators found that EETs accelerated tissue growth and organ regeneration during liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. They observed the same outcomes when they administered synthetic EETs and saw delayed tissue regeneration when EET levels were genetically or pharmacologically lowered. Soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promoted liver and lung regeneration.
Citation: Panigrahy D, Kalish BT, Huang S, Bielenberg DR, Le HD, Yang J, Edin ML, Lee CR, Benny O, Mudge DK, Butterfield CE, Mammoto A, Mammoto T, Inceoglu B, Jenkins RL, Simpson MA, Akino T, Lih FB, Tomer KB, Ingber DE, Hammock BD, Falck JR, Manthati VL, Kaipainen A, D'Amore PA, Puder M, Zeldin DC, Kieran MW. 2013. Epoxyeicosanoids promote organ and tissue regeneration. Proc Natl Acad Sci U S A 110(33):13528-13533.