title: Effects of the novel compound DK223 ([1E,2E-1,2-Bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) on migration and proliferation of human keratinocytes and primary dermal fibroblasts.
abstract: Wound healing plays an important role in protecting the human body from external infection. Cell migration and proliferation of keratinocytes and dermal fibroblasts are essential for proper wound healing. Recently, several studies have demonstrated that secondary compounds produced in plants could affect skin cells migration and proliferation. In this study, we identified a novel compound DK223 ([1E,2E-1,2-bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) that concomitantly induced human keratinocyte migration and dermal fibroblast proliferation. We evaluated the regulation of epithelial and mesenchymal protein markers, such as E-cadherin and Vimentin, in human keratinocytes, as well as extracellular matrix (ECM) secretion and metalloproteinase families in dermal fibroblasts. DK223 upregulated keratinocyte migration and significantly increased the epithelial marker E-cadherin in a time-dependent manner. We also found that reactive oxygen species (ROS) increased significantly in keratinocytes after 2 h of DK223 exposure, returning to normal levels after 24 h, which indicated that DK223 had an early shock effect on ROS production. DK223 also stimulated fibroblast proliferation, and induced significant secretion of ECM proteins, such as collagen I, III, and fibronectin. In dermal fibroblasts, DK223 treatment induced TGF-β1, which is involved in a signaling pathway that mediates proliferation. In conclusion, DK223 simultaneously induced both keratinocyte migration via ROS production and fibroblast proliferation via TGF-β1 induction.
authors: Department of Biochemistry, School of Medicine, Jeju National University, Jeju 690-756, Korea. homanhtin@gmail.com.
authors: Manh Tin
authors: MT
authors: Ho
authors: Department of Pediatrics, School of Medicine, Jeju National University, Jeju 690-756, Korea. medyapsb@naver.com.
authors: Hyun Sik
authors: HS
authors: Kang
authors: Department of Urology, School of Medicine, Jeju National University, Jeju 690-756, Korea. urohjs@jejunu.ac.kr.
authors: Jung Sik
authors: JS
authors: Huh
authors: Department of Biochemistry, School of Medicine, Jeju National University, Jeju 690-756, Korea. biochem310@jejunu.ac.kr.
authors: Young Mee
authors: YM
authors: Kim
authors: Division of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea. yoongho@konkuk.ac.kr.
authors: Yoongho
authors: Y
authors: Lim
authors: Department of Biochemistry, School of Medicine, Jeju National University, Jeju 690-756, Korea. moonjcho@jejunu.ac.kr.
authors: Moonjae
authors: M
authors: Cho
mesh_terms: D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: C000596021:(1,2-bis(6-methoxy-2H-chromen-3-yl)methylene)hydrazine; D001578:Benzopyrans; D015820:Cadherins; D024042:Collagen Type I; D024061:Collagen Type III; D005353:Fibronectins; D006834:Hydrazines; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D014746:Vimentin; C029424:hydrazine