Abstract
Pressure-induced vasodilation (PIV) delays the decrease in cutaneous blood flow produced by local application of low pressure to the skin, a physiologically appropriate adjustment of local vasomotor function. Individuals without a normal PIV response have a high risk of ulceration. Here we demonstrate that acid-sensing ion channel 3 (Asic3) is an essential neuronal sensor for the vasodilation response to direct pressure in both humans and rodents and for protecting against pressure ulcers in mice.
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References
Allman, R.M. N. Engl. J. Med. 320, 850–853 (1989).
Lyder, C.H. J. Am. Med. Assoc. 289, 223–226 (2003).
Reddy, M. et al. J. Am. Med. Assoc. 300, 2647–2662 (2008).
Fromy, B., Merzeau, S., Abraham, P. & Saumet, J.L. Br. J. Pharmacol. 131, 1161–1171 (2000).
Fromy, B. et al. J. Invest. Dermatol. 130, 849–855 (2010).
Koïtka, A. et al. Diabetes 53, 721–725 (2004).
Waldmann, R. et al. J. Biol. Chem. 272, 20975–20978 (1997).
Waldmann, R., Champigny, G., Bassilana, F., Heurteaux, C. & Lazdunski, M. Nature 386, 173–177 (1997).
Drew, L.J. et al. J. Physiol. (Lond.) 556, 691–710 (2004).
Arnadóttir, J. & Chalfie, M. Annu. Rev. Biophys. 39, 111–137 (2010).
Deval, E. et al. Pharmacol. Ther. 128, 549–558 (2010).
Price, M.P. et al. Neuron 32, 1071–1083 (2001).
Page, A.J. et al. Gut 54, 1408–1415 (2005).
Molliver, D.C. et al. Mol. Pain 1, 35 (2005).
Deval, E. et al. EMBO J. 27, 3047–3055 (2008).
Jones, N.G., Slater, R., Cadiou, H., McNaughton, P. & McMahon, S.B. J. Neurosci. 24, 10974–10979 (2004).
Immke, D.C. & McCleskey, E.W. Nat. Neurosci. 4, 869–870 (2001).
Allman, R.M., Goode, P.S., Burst, N., Bartolucci, A.A. & Thomas, D.R. Adv. Wound Care 12, 22–30 (1999).
Wultsch, T. et al. Pain 134, 245–253 (2008).
Deval, E. et al. J. Neurosci. 31, 6059–6066 (2011).
Diochot, S. et al. EMBO J. 23, 1516–1525 (2004).
Diochot, S., Salinas, M., Baron, A., Escoubas, P. & Lazdunski, M. Toxicon 49, 271–284 (2007).
Voilley, N., de Weille, J., Mamet, J. & Lazdunski, M. J. Neurosci. 21, 8026–8033 (2001).
Dubé, G.R. et al. Pain 117, 88–96 (2005).
Jones, N.G., Slater, R., Cadiou, H., McNaughton, P. & McMahon, S.B. J. Neurosci. 24, 10974–10979 (2004).
Costa, R. et al. Br. J. Pharmacol. 154, 1094–1103 (2008).
Demiot, C. et al. Diabetes 55, 1478–1483 (2006).
Sigaudo-Roussel, D. et al. Diabetes 53, 1564–1569 (2004).
Fromy, B., Abraham, P. & Saumet, J.L. Brain Res. Brain Res. Protoc. 5, 198–203 (2000).
Fromy, B., Abraham, P. & Saumet, J.L. Brain Res. 811, 166–168 (1998).
Potter, C. & Harris, A.L. Cell Cycle 3, 164–167 (2004).
Wykoff, C.C. et al. Cancer Res. 60, 7075–7083 (2000).
Acknowledgements
We would like to thank the subjects who participated in this study. We thank C. Viart-Ferber, A. Josset-Lamaugarny, G. James and N. Plèche (AnexPeau facility, Lyon) for helpful assistance in human and rodent studies. We are very grateful to S. Diochot and E. Deval (CNRS UMR 7275) for providing APETx2 and knockout mice, to P. Inquimbert, V. Friend (CNRS UMR 7275) and N. Gadot (Anipath facility, Lyon) for histological studies, and to R. Buttin and D. Katz for technical support for Perimed equipment. We also thank Fondation pour la Recherche Médicale and Prevention Education Recherche Soins Escarres for financial support.
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B.F., J.L.S. and M.L. conceived of and designed the experiments, analyzed the data, and contributed to writing and editing the manuscript; B.F. performed the experiments; E.L. and D.S.-R. contributed to discussions and provided tools important for completion of the work.
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Fromy, B., Lingueglia, E., Sigaudo-Roussel, D. et al. Asic3 is a neuronal mechanosensor for pressure-induced vasodilation that protects against pressure ulcers. Nat Med 18, 1205–1207 (2012). https://doi.org/10.1038/nm.2844
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DOI: https://doi.org/10.1038/nm.2844
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