Rhamm mimetic peptide blocks hyaluronan fragment signaling and promotes skin excisional wound repair by reducing inflammation

Tolg, C.; Telmer, P.; Ma, J.; Akentieva, N.P.; Luyt, L.G.; Turley, E.A.

Авторы: Tolg C., Telmer P., Ma J., Akentieva N.P., Luyt L.G., Turley E.A.
Журнал: American Journal of Pathology
Том: 181
Номер: 4
Год издания: 2012
Издательство: American Society for Investigative Pathology
Местоположение издательства: United States
Первая страница: 1250
Последняя страница: 1270
Аннотация: Hyaluronan is activated by fragmentation and con-trols inflammation and fibroplasia during wound repair and diseases (eg, cancer). Hyaluronan-binding peptides were identified that modify fibrogenesis during skin wound repair. Peptides were selected from 7-to 15mer phage display libraries by panning with hyaluronan-Sepharose beads and assayed for their ability to block fibroblast migration in response tohyaluronan oligosaccharides (10 kDa). A 15mer pep-tide (P15-1), with homology to receptor for hyaluronan mediated motility (RHAMM) hyaluronan binding sequences, was the most effective inhibitor. P15-1 bound to 10-kDa hyaluronan with and appeared to specifically mimic RHAMM since itsignificantly reduced binding of hyaluronan oligosaccharides to recombinant RHAMM but not to recombinant CD44 or TLR2,4, and altered wound repair in wild-type but not RHAMM-/- mice. One topical application of P15-1 to full-thickness excisional rat wounds significantly reducedwound macrophage number, fibroblast number, andblood vessel density compared to scrambled, negative control peptides. Wound collagen 1, transforming growth factor-1, and smooth muscle actin were reduced, whereas tenascin C was increased, suggesting that P15-1 promoted a form of scarless healing. Signaling/microarray analyses showed that P15-1 blocks RHAMM-regulatedfocal adhesion kinase pathways in fibroblasts. These results identify a new class of reagents that attenuate proinflammatory, fibrotic repair by blocking hyaluronan oligosaccharide signaling.
Добавил в систему: Акентьева Наталья Павловна

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Rhamm mimetic peptide blocks hyaluronan fragment signaling and promotes skin excisional wound repair by reducing inflammationстатья

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