Acceleration of cutaneous wound healing by brassinosteroids
Authors
Debora Esposito, Thirumurugan Rathinasabapathy, Barbara Schmidt, Michael P. Shakarjian, Slavko Komarnytsky, Ilya Raskin
Institution
Rutgers
Country
United States
Year
2013
Journal
Wound Repair and Regeneration
Abstract
Brassinosteroids are plant growth hormones involved in cell growth, division, and
differentiation. Their effects in animals are largely unknown, although recent studies
showed that the anabolic properties of brassinosteroids are possibly mediated through
the phosphoinositide 3-kinase/protein kinase B signaling pathway. Here, we examined
biological activity of homobrassinolide (HB) and its synthetic analogues in in
vitro proliferation and migration assays in murine fibroblast and primary keratinocyte
cell culture. HB stimulated fibroblast proliferation and migration and weakly induced
keratinocyte proliferation in vitro. The effects of topical HB administration on progression
of wound closure were further tested in the mouse model of cutaneous
wound healing. C57BL/6J mice were given a full-thickness dermal wound, and the
rate of wound closure was assessed daily for 10 days, with adenosine receptor agonist
CGS-21680 as a positive control. Topical application of brassinosteroid significantly
reduced wound size and accelerated wound healing in treated animals. mRNA levels
of transforming growth factor beta and intercellular adhesion molecule 1 were
significantly lower, while tumor necrosis factor alpha was nearly suppressed in
the wounds from treated mice. Our data suggest that topical application of
brassinosteroids accelerates wound healing by positively modulating inflammatory
and reepithelialization phases of the wound repair process, in part by enhancing Akt
signaling in the skin at the edges of the wound and enhancing migration of fibroblasts
in the wounded area. Targeting this signaling pathway with brassinosteroids may
represent a promising approach to the therapy of delayed wound healing.