title: Xiamenmycin attenuates hypertrophic scars by suppressing local inflammation and the effects of mechanical stress.
abstract: Hypertrophic scarring is a common disease affecting millions of people around the world, but there are currently no satisfactory drugs to treat the disease. Exaggerated inflammation and mechanical stress have been shown to be two main mechanisms of excessive fibrotic diseases. Here we found that a benzopyran natural product, xiamenmycin, could significantly attenuate hypertrophic scar formation in a mechanical stretch-induced mouse model. The compound suppressed local inflammation by reducing CD4+ lymphocyte and monocyte/macrophage retention in fibrotic foci and blocked fibroblast adhesion with monocytes. Both in vivo and in vitro studies found that the compound inhibited the mechanical stress-induced profibrotic effects by suppressing proliferation, activation, fibroblast contraction, and inactivating FAK, p38, and Rho guanosine triphosphatase signaling. Taken together, the compound could simultaneously suppress both the inflammatory and mechanical stress responses, which are the two pivotal pathological processes in hypertrophic scar formation, thus suggesting that xiamenmycin can serve as a potential agent for treating hypertrophic scar formation and other excessive fibrotic diseases.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiao-Jin
authors.initials: XJ
authors.lastname: Liu
authors.forename: Min-Juan
authors.initials: MJ
authors.lastname: Xu
authors.forename: Si-Teng
authors.initials: ST
authors.lastname: Fan
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Yang
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D013912:Threonine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001578:Benzopyrans; C582113:N-((3,4-dihydro-3-hydroxy-2-methyl-2-(4'-methyl-3'-pentenyl)-2H-1-benzopyran-6-yl)carbonyl)threonine; D013912:Threonine; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D020764:cdc42 GTP-Binding Protein