B1 repetitive sequence methylation enhances wound healing of second-degree burns in rats

Abstract

The accumulation of DNA damage in burn wounds delays wound healing. DNA methylation by short interspersed nuclear element (SINE) small interfering (si) RNA prevents DNA damage and promotes cell proliferation. Therefore, SINE siRNA may be able to promote burn wound healing. Here, a SINE B1 siRNA was used to treat burn wounds in rats. Second-degree burn wounds were introduced on the backs of rats. The rats were then divided into three groups: a B1 siRNA-treated, saline-treated control, and saline + calcium phosphate-nanoparticle-treated control group (n=15/group). The wounds were imaged on days 0, 7, 14, 21 and 28 post-injury. The tissue sections were processed for methylation, histological and immunohistochemical examination, and scored based on the overall expression of histone H2AX phosphorylated on serine 139 (γH2AX) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Burn wound closure improved in the B1 siRNA-treated group compared with that in the control group, especially from days 14-28 post-injury (P<0.001). The overall pathological score and degree of B1 methylation in the B1 siRNA-treated group improved significantly at days 14-28 post-injury, with the maximum improvement observed on day 14 (P<0.01) compared with the NSS and Ca-P nanoparticle groups. Immunohistochemical staining revealed lower expression of γH2AX and 8-OHdG in the B1 siRNA-treated group than in the control groups at days 14-28 post-injury; the maximum improvement was observed on days 14 and 21. These data imply that administering SINE siRNA is a promising therapeutic option for managing second-degree burns.