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Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release
Author(s) -
AgouTii Abdelali,
Ahmed Mostefai H.,
Porro Chiarra,
Carusio Nunzia,
Favre Julie,
Richard Vincent,
Henrion Daniel,
Carmen Martinez M.,
Andriantsitohaina Ramaroson
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-8079com
Subject(s) - cyclopamine , sonic hedgehog , patched , nitric oxide , microbiology and biotechnology , chemistry , hedgehog signaling pathway , mapk/erk pathway , pharmacology , cancer research , signal transduction , biochemistry , biology , organic chemistry
Microparticles (MPs) are small fragments generated from the plasma membrane after cell stimulation. Among the candidate proteins harbored by MPs, we recently showed that sonic hedgehog (Shh) is present in MPs generated from activated/apoptotic human T lymphocytes [Martinez et al., Blood (2006) vol. 108, 3012–3020]. We show here that Shh carried by MPs induces nitric oxide (NO) release from endothe‐lial cells, triggers changes in the expression and phos‐phorylation of enzymes related to the NO pathway, and decreases production of reactive oxygen species. When PI3‐kinase and ERK signaling were specifically inhibited, the effects of MPs were reversed. In vivo injection of MPs in mice was also able to improve endothelial function by increasing NO release, and it reversed endothelial dysfunction after ischemia/reperfusion. Silencing the effects of Shh with cyclopamine, a specific inhibitor of Shh, or siRNA, an inhibitor of the Shh receptor Patched, strongly reduced production of NO elicited by MPs. Taken together, we propose that the biological message carried by MPs harboring Shh may represent a new therapeutic approach against endothe‐lial dysfunction during acute severe endothelial injury.—Agouni A., Mostefai, H. A., Porro, C., Carusio, N., Favre, J., Richard, V., Henrion, D., Martinez, M. C., Andriantsitohaina R. Sonic hedgehog carried by micro‐particles corrects endothelial injury through nitric oxide release. FASEB J. 21, 2735–2741 (2007)