Department of Biochemistry, School of Medicine, Jeju National University, Jeju 690-756, Korea.
Department of Pathology, School of Medicine, Jeju National University, Jeju 690-756, Korea.
Int J Mol Sci. 2018 Apr 11;19(4):1164. doi: 10.3390/ijms19041164.
Cutaneous wound repair is an intricate process whereby the skin reprograms itself after injury. In the mid-phase of wound repair, the proliferation, migration, and differentiation of cells are the major mechanisms to lead remodeling. We investigated the effect of BMM ((1E,2E)-1,2-bis((6-bromo-2H-chromen-3-yl)methylene)hydrazine), a novel synthetic material, on the migration and viability of keratinocytes or fibroblasts using the in vitro scratch woundhealing, electric cell-substrate imedance sensing (ECIS), invasion, and MTT assays. Cell migration-related factors were analyzed using western blot, and we found that treatment with BMM stimulated the EMT pathway and focal adhesion kinase (FAK)/Src signaling. Differentiation of HaCaT keratinocyte and fibroblast cells was also stimulated by BMM and specifically, NOX2/4 contributed to the activation of fibroblasts for wound healing. Furthermore, BMM treated HaCaT keratinocyte and fibroblast-co-cultured cells increased migration and differentiation. TGF-β and Cyr61 were also secreted to a greater extent than in single cultured cells. In vivo experiments showed that treatment with BMM promotes wound closure by promoting re-epithelialization. In this study, we demonstrated that a novel synthetic material, BMM, is capable of promoting wound healing via the stimulation of re-epithelialization in the epidermis and the activation of fibroblasts in the dermis, in particular, via the acceleration of the interaction between the epidermis and dermis.
皮肤创伤修复是一个复杂的过程，皮肤在受伤后会重新编程。在创伤修复的中期，细胞的增殖、迁移和分化是导致重塑的主要机制。我们使用体外划痕愈合、电细胞-底物阻抗传感（ECIS）、侵袭和 MTT 测定法，研究了一种新型合成材料 BMM((1E,2E)-1,2-双((6-溴-2H-色烯-3-基)亚甲基)肼)对角质形成细胞或成纤维细胞迁移和活力的影响。通过 Western blot 分析细胞迁移相关因子，我们发现 BMM 处理刺激 EMT 途径和焦点黏附激酶（FAK）/Src 信号。BMM 还刺激 HaCaT 角质形成细胞和成纤维细胞的分化，并且 NOX2/4 有助于成纤维细胞的伤口愈合激活。此外，BMM 处理的 HaCaT 角质形成细胞和成纤维细胞共培养细胞增加了迁移和分化。TGF-β和 Cyr61 的分泌也比在单一培养细胞中更多。体内实验表明，BMM 的治疗通过促进表皮的再上皮化来促进伤口闭合。在这项研究中，我们证明了一种新型合成材料 BMM 能够通过刺激表皮的再上皮化和真皮中成纤维细胞的激活来促进伤口愈合，特别是通过加速表皮和真皮之间的相互作用。
