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Targeting the neuropilin-2 receptor signaling axis

Neuropilin-2 (NRP-2), expressed in capillaries and smooth muscle, is involved in a signaling axis featuring both stimulatory and inhibitory pathways. Ligand interaction with NRP-2 determines the effectual pathway: stimulatory VEGF, or inhibitory Semaphorin3. VEGF interaction causes NRP-2 localization with VEGFR-2, while Semaphorin3 (SEMA3) interaction causes NRP-2 to complex with Plexin A. VEGFR-2 interaction induces permeability and angiogenesis, making this an attractive target for anti-angiogenesis treatment. Plexin A interaction induces smooth muscle relaxation, offering a target for treatment of loss of bladder contractility. We aimed to further our understanding of the necessity of NRP-2 in the VEGFR-2-mediated induction of angiogenesis and permeability by performing assays in Nrp-2 knockout (KO) mice. We also tested an inhibitor against Semaphorin3/NRP-2 binding using U87MG cell, a human glioblastoma cell line. Angiogenesis assays were largely inconclusive, but suggested that NRP-2 does play a substantial role in contributing towards vessel growth. Permeability assays showed that NRP-2 plays a significant role in induction of permeability. The Semaphorin3F/NRP-2 inhibitor showed promise as a potential therapeutic, limiting the extent of Semaphorin3-based inhibition of VEGFR-2 pathway. / 2026-02-12T00:00:00Z

Identiferoai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48091
Date13 February 2024
CreatorsAshok, Karthik
ContributorsHeaphy, Christopher, Bielenberg, Diane R.
Source SetsBoston University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation

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