Vascular endothelial growth factor accelerates compensatory lung growth after unilateral pneumonectomy

Sakurai, Maromi K.; Lee, Sang; Arsenault, Danielle; Nosé, Vânia; Wilson, Jay M.; Heymach, John V.; Puder, Mark

doi:10.1152/ajplung.00064.2006

Cited by 68 publications

(66 citation statements)

References 36 publications

(37 reference statements)

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“…VEGF, but not FGF-2, accelerates compensatory lung growth after unilateral pneumonectomy (40). However, two selective VEGF receptor inhibitors had no effect on lung regeneration, suggesting that VEGF is not the only regulator of tissue regeneration (40).…”

Section: Discussionmentioning

confidence: 99%

“…Our data suggest that EETs also play an important role in lung tissue repair. Impaired lung regeneration is present in life-threatening diseases such as bronchopulmonary dysplasia and congenital diaphragmatic hernia in premature infants (40). Several studies support the notion that ECs within the lungs actively promote normal alveolar growth and lung regeneration (15).…”

Section: Discussionmentioning

confidence: 99%

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Epoxyeicosanoids promote organ and tissue regeneration

Panigrahy

Kalish

Huang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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127

124

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epoxyeicosanoids promote organ and tissue regeneration

Panigrahy

Kalish

Huang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

127

124

View full text Add to dashboard Cite

show abstract

“…Other researchers have shown the effects of exogenous angiogenic factors, such as vascular endothelial growth factor (VEGF) in the mouse model. Additional VEGF therapy accelerated the CLG response, which was completed in only 4 days compared to 10 days in the pneumonectomy control group (Sakurai, et al, 2007).…”

Section: Vascular Growth and Angiogenesismentioning

confidence: 96%

“…Researchers described the effects of exogenous VEGF in the mouse model, showing that exogenous VEGF therapy accelerated the CLG response, which was completed in only 4 days compared to 10 days in control animals. However, these effects could not be blocked by the use of either VEGF receptor inhibitors or neutralizing antibodies (Sakurai, et al, 2007). Another study associated lung expansion and other signaling pathways to VEGF.…”

Section: Vascular Endothelial Growth Factor (Vegf)mentioning

confidence: 99%

Compensatory Lung Growth After Pneumonectomy

Fernández¹,

Isbell²,

Jones³

et al. 2012

Topics in Thoracic Surgery

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“…Newly formed vasculatures in the lung not only deliver oxygen, nutrients and various cell components required for organ formation, but also provide instructive regulatory signals to surrounding cells [22][23][24][25] . Thus, angiogenesis plays key roles in regenerative alveolarization in adult lungs 24,26,27 . In addition, deregulated angiogenesis contributes to chronic lung diseases such as chronic obstructive pulmonary disease (COPD) .…”

Section: Introductionmentioning

confidence: 99%

Implantation of Fibrin Gel on Mouse Lung to Study Lung-specific Angiogenesis

Mammoto

2014

JoVE

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Recent significant advances in stem cell research and bioengineering techniques have made great progress in utilizing biomaterials to regenerate and repair damage in simple tissues in the orthopedic and periodontal fields. However, attempts to regenerate the structures and functions of more complex three-dimensional (3D) organs such as lungs have not been very successful because the biological processes of organ regeneration have not been well explored. It is becoming clear that angiogenesis, the formation of new blood vessels, plays key roles in organ regeneration. Newly formed vasculatures not only deliver oxygen, nutrients and various cell components that are required for organ regeneration but also provide instructive signals to the regenerating local tissues. Therefore, to successfully regenerate lungs in an adult, it is necessary to recapitulate the lung-specific microenvironments in which angiogenesis drives regeneration of local lung tissues. Although conventional in vivo angiogenesis assays, such as subcutaneous implantation of extracellular matrix (ECM)-rich hydrogels (e.g., fibrin or collagen gels or Matrigel -ECM protein mixture secreted by Engelbreth-Holm-Swarm mouse sarcoma cells), are extensively utilized to explore the general mechanisms of angiogenesis, lung-specific angiogenesis has not been well characterized because methods for orthotopic implantation of biomaterials in the lung have not been well established. The goal of this protocol is to introduce a unique method to implant fibrin gel on the lung surface of living adult mouse, allowing for the successful recapitulation of host lung-derived angiogenesis inside the gel. This approach enables researchers to explore the mechanisms by which the lung-specific microenvironment controls angiogenesis and alveolar regeneration in both normal and pathological conditions. Since implanted biomaterials release and supply physical and chemical signals to adjacent lung tissues, implantation of these biomaterials on diseased lung can potentially normalize the adjacent diseased tissues, enabling researchers to develop new therapeutic approaches for various types of lung diseases. Video LinkThe video component of this article can be found at

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Vascular endothelial growth factor accelerates compensatory lung growth after unilateral pneumonectomy

Abstract: Sakurai MK, Lee S, Arsenault DA, Nose V, Wilson JM, Heymach JV, Puder M. Vascular endothelial growth factor accelerates compensatory lung growth after unilateral pneumonectomy.

Cited by 68 publications

References 36 publications

Epoxyeicosanoids promote organ and tissue regeneration

Epoxyeicosanoids promote organ and tissue regeneration

Compensatory Lung Growth After Pneumonectomy

Implantation of Fibrin Gel on Mouse Lung to Study Lung-specific Angiogenesis

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