Vascular Endothelial Growth Factor as an Immediate-Early Activator of Ultraviolet-Induced Skin Injury

Stella P. Hartono, Victoria M. Bedell, Sk Kayum Alam, Madelyn O'Gorman, Ma Kayla Serres, Stephanie R. Hall, Krishnendu Pal, Rachel A. Kudgus, Priyabrata Mukherjee, Davis M. Seelig, Alexander Meves, Debabrata Mukhopadhyay, Stephen C. Ekker, Luke H. Hoeppner

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

Abstract

The negative health consequences of acute ultraviolet (UV) exposure are evident, with reports of 30,000 emergency room visits annually to treat the effects of sunburn in the United States alone. The acute effects of sunburn include erythema, edema, severe pain, and chronic overexposure to UV radiation, leading to skin cancer. Whereas the pain associated with the acute effects of sunburn may be relieved by current interventions, existing post-sunburn treatments are not capable of reversing the cumulative and long-term pathological effects of UV exposure, an unmet clinical need. Here we show that activation of the vascular endothelial growth factor (VEGF) pathway is a direct and immediate consequence of acute UV exposure, and activation of VEGF signaling is necessary for initiating the acute pathological effects of sunburn. In UV-exposed human subjects, VEGF signaling is activated within hours. Topical delivery of VEGF pathway inhibitors, targeted against the ligand VEGF-A (gold nanoparticles conjugated with anti-VEGF antibodies) and small-molecule antagonists of VEGF receptor signaling, prevent the development of erythema and edema in UV-exposed mice. These findings collectively suggest targeting VEGF signaling may reduce the subsequent inflammation and pathology associated with UV-induced skin damage, revealing a new postexposure therapeutic window to potentially inhibit the known detrimental effects of UV on human skin. It is essential to emphasize that these preclinical studies must not be construed as suggesting in any way the use of VEGF inhibitors as a sunburn treatment in humans because warranted future clinical studies and appropriate agency approval are essential in that regard.

Original languageEnglish (US)
Pages (from-to)154-164
Number of pages11
JournalMayo Clinic Proceedings
Volume97
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding Information:
Grant Support: This study was supported by National Institutes of Health grants DK083219 (to V.M.B.), CA215105 (to A.M.), CA78383 (to D.M.), CA150190 (to D.M.), GM63904 (to S.C.E.), and CA187035 (to L.H.H.) as well as Fifth District Eagles Cancer Telethon Postdoctoral Fellowship Award (to S.K.A.), Institutional Research Grant #129819-IRG-16-189-58-IRG81 from the American Cancer Society (to L.H.H.), Austin, Minnesota “Paint the Town Pink” Award (to L.H.H.), The Mayo Foundation , and The Hormel Foundation .

Publisher Copyright:
© 2021 The Authors

Fingerprint

Dive into the research topics of 'Vascular Endothelial Growth Factor as an Immediate-Early Activator of Ultraviolet-Induced Skin Injury'. Together they form a unique fingerprint.

Cite this