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Inhibition of Neurite Outgrowth by a Neuropilin-1 Binding Peptide Derived from Semaphorin 3A

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Abstract

Semaphorin 3A (Sema3A), an axon guidance molecule, inhibits neurite outgrowth of sensory neurons. Recombinant Sema3A protein has also inhibited scratching behavior and improved skin inflammation in an atopic dermatitis model. In the present study, we investigated whether Sema3A-derived peptides could bind its receptor, neuropilin-1 (NRP1), to inhibit neurite outgrowth. Here, two candidate NRP1-binding (NPB) peptides, NPB7 and NPB15, were found to inhibit NGF-induced survival and neurite outgrowth of PC12 cells and rat primary neurons in serum-free medium. To investigate the preventive effect of the two NPB peptides in vivo, we assessed whether they could inhibit skin inflammation induced by repeated topical application of oxazolone in mice. NPB15 peptide, but not NPB7, inhibited ear swelling. The NPB15 peptide solution and Vaseline ointment groups showed slightly decreased epidermal nerve densities compared with controls. The combination of NPB15 peptide and Vaseline ointment increased the inhibitory effect of NPB15 peptide on epidermal nerve densities. These results suggest that Sema3A-derived peptides can bind to NRP1 and inhibit neurite outgrowth both in vitro and in vivo. Thus, these peptides may be potent candidates for the treatment of atopic dermatitis.

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Abbreviations

AD:

Atopic dermatitis

cGMP:

Cyclic guanosine monophosphate

END:

Epidermal nerve density

FBS:

Fetal bovine serum

NGF:

Nerve growth factor

NPB:

NRP1-binding

NRP1:

Neuropilin-1

OCD:

Oxazolone-induced chronic dermatitis

rhNRP1:

Recombinant human NRP1

rhSema3A:

Recombinant human semaphorin 3A/Fc chimera

Sema3A:

Semaphorin 3A

SPR:

Surface plasmon resonance

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Acknowledgments

We thank Keiko Shimoura and Kumi Kodama (Department of Pharmacoepidemiology, Kyoto University) for technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Authors and Affiliations

  1. Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshidakonoecho, Sakyoku, Kyoto, 606-8501, Japan

    Masayuki Kohno, Koji Ohara, Tomohisa Horibe & Koji Kawakami

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  1. Masayuki Kohno
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  2. Koji Ohara
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  3. Tomohisa Horibe
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  4. Koji Kawakami
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Corresponding author

Correspondence to Koji Kawakami.

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Fig. S1

Schematic illustration of the in vivo experimental protocol. a Comparison study between NPB15 and NPB7 peptides. b Comparison of treatment efficacy of NPB15 between an ethanol solution and Vaseline ointment (TIFF 41 kb)

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Kohno, M., Ohara, K., Horibe, T. et al. Inhibition of Neurite Outgrowth by a Neuropilin-1 Binding Peptide Derived from Semaphorin 3A. Int J Pept Res Ther 20, 153–160 (2014). https://doi.org/10.1007/s10989-013-9379-3

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