[Molecular mechanism of olfaetomedin 4 involved in inflammatory reaction after severe burn through SIRT1/PGC-1α signal pathway].

Objective To explore the molecular mechanism of olfaetomedin 4(OLFM4) participating in inflammatory reaction after severe burns through deacetylase Sirtuin 1/peroxisome proliferator-activated receptor γ coactivator 1α(SIRT1/PGC-1α) signaling pathway. Methods Human skin fibroblasts (HSFs) were divided into control group, heat injury group, heat injury+OLFM4 group, heat injury+sh-SIRT1 group, heat injury+sh-OLFM4 group and heat injury+OLFM4+sh-SIRT1 group. Thermal injury was induced by incubating the cell suspension in water at 52 DegreesCelsius for 30 s. The proliferation ability of cells was investigated by CCK-8 and EdU staining, and the migration ability of cells was investigated by scratch test. Mice were randomly divided into model group, sh-SIRT1 group, OLFM4 group and OLFM4+sh-SIRT1 group, with 6 mice in each group. Each group of mice was used to establish a full-thickness skin burn model with 30% of total surface area. Sh-SIRT1, OLFM4 and OLFM4+sh-SIRT1 were injected intradermally into mice in sh-SIRT1 group, OLFM4 group and OLFM4+sh-SIRT1 group respectively at the burn edge. On the 4th, 8th and 16th day after injection, the wound healing was observed and recorded, and the healed tissues were collected for analysis. Results Compared with the control group, the heat injury group exhibited significantly reduced cell viability, decreased number of EdU-positive cells, impaired cell migration, and diminished expression of SIRT1 and PGC-1α proteins in HSFs. Compared with the heat injury group, the heat injury+OLFM4 group showed a significant increase in HSF cell viability, number of EdU-positive cells, cell migration, and expression of SIRT1 and PGC-1α proteins, whereas the heat injury+sh-OLFM4 group exhibited a further decrease in these parameters. Compared with heat injury+OLFM4 group, the number of EdU positive cells and cell migration of HSFs in heat injury+OLFM4+sh-SIRT1 group decreased significantly. Compared with the model group, the expressions of OLFM4, SIRT1 and PGC-1α protein in OLFM4 group increased significantly, and the wound healing speed was significantly accelerated. Compared with OLFM4 group, the expressions of SIRT1 and PGC-1α protein in OLFM4+sh-SIRT1 group decreased significantly, and the wound healing speed was significantly reduced. Compared with the model group, the mRNA expression levels of TNF-α, IL-1β and IL-6 in OLFM4 group decreased significantly, and the mRNA expression levels of TNF-α, IL-1β and IL-6 in sh-SIRT1 group increased significantly. Compared with OLFM4 group, the mRNA expression levels of TNF-α, IL-1β and IL-6 in OLFM4+sh-SIRT1 group increased significantly. Conclusions Up-regulation of OLFM4 promotes the proliferation and migration of HSFs, and local up-regulation of OLFM4 accelerates the healing speed of skin wounds in mice and reduces the inflammatory reaction of the healing tissues of burn wounds in the inflammatory stage.This mechanism may is likely associated with the activation of SIRT1/PGC-1α signaling pathway.