Periplaneta americana L. extract promotes infectious diabetic ulcers wound healing by downregulation of LINC01133/ SLAMF9

Background: Wound healing in diabetic ulcers remains a great challenge, while bacterial infection and poor angiogenesis are considered as the principal contributing factors. Periplaneta americana L. Extract (PAE) has been extensively applied for the treatment of diabetic wound healing, however, the potential mechanisms remain ambiguous. Methods: Long non-coding RNAs (lncRNAs) expressions were analyzed by high-throughput sequencing in wound tissues from diabetic anal fistula patients with or without PAE treatment. Peripheral blood monocytes from patients were differentiated into M0 macrophages with human macrophage colony-stimulating factor (hM-CSF), then M1 macrophages was induced by lipopolysaccharide. Macrophage markers were detected by flow cytometry. Cell viability, migration and angiogenic capacity of human umbilical vein endothelial cells (HUVEC) co-cultured with macrophages were assessed using CCK-8, cell scratch and tube formation assays. RIP and RNA pull-down were operated for confirming interactions between genes. Results: LINC01133 and SLAMF9 were downregulated in wound tissues of PAE-treated patients. PAE suppressed M1 macrophage polarization and promoted HUVEC proliferation, migration and angiogenesis, which were weakened by overexpression of LINC01133 or SLAMF9. LINC01133 upregulated SLAMF9 through interacting with ELAVL1. SLAMF9 overexpression overturned the effects of LINC01133 silencing on macrophage polarization and HUVEC. Conclusion: PAE promoted wound healing of infectious diabetic ulcers by downregulating LINC01133/SLAMF9.