Department of Anorectal Disease 1, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha 410005, China.
Department of Anorectal Disease 1, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha 410005, China; Laboratory of Vascular Biology and Translational Medicine, Medical School, Hunan University of Chinese Medicine/Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine, Changsha 410208, China.
Chin J Nat Med. 2024 Jul;22(7):608-618. doi: 10.1016/S1875-5364(24)60569-8.
Wound healing in diabetic ulcers remains a significant clinical challenge, primarily due to bacterial infection and impaired angiogenesis. Periplaneta americana extract (PAE) has been widely used to treat diabetic wounds, yet its underlying mechanisms are not fully understood. This study aimed to elucidate these mechanisms by analyzing long non-coding RNA (lncRNA) expressions in the wound tissues from diabetic anal fistula patients treated with or without PAE, using high-throughput sequencing. Peripheral blood monocytes from patients were differentiated into M0 macrophages with human macrophage colony-stimulating factor (hM-CSF) and subsequently polarized into M1 macrophages with lipopolysaccharide. The results indicated that LINC01133 and SLAMF9 were downregulated in wound tissues of patients treated with PAE. Furthermore, PAE suppressed M1 macrophage polarization and enhanced human umbilical vein endothelial cell (HUVEC) proliferation, migration, and angiogenesis. These effects were diminished when LINC01133 or SLAMF9 were overexpressed. Mechanistically, LINC01133 was shown to upregulate SLAMF9 through interaction with ELAVL1. Overexpression of SLAMF9 reversed the effects of LINC01133 silencing on macrophage polarization and HUVEC functions. In conclusion, PAE facilitates the healing of infected diabetic ulcers by downregulating the LINC01133/SLAMF9 pathway.
糖尿病性溃疡的愈合仍然是一个重大的临床挑战，主要是由于细菌感染和血管生成受损。美洲大蠊提取物（PAE）已被广泛用于治疗糖尿病性伤口，但其潜在机制尚不完全清楚。本研究旨在通过对糖尿病性肛瘘患者经或未经 PAE 治疗后的伤口组织进行高通量测序，分析长链非编码 RNA（lncRNA）的表达，阐明这些机制。用人巨噬细胞集落刺激因子（hM-CSF）将患者外周血单核细胞分化为 M0 巨噬细胞，然后用脂多糖将其极化为 M1 巨噬细胞。结果表明，PAE 治疗的患者伤口组织中 LINC01133 和 SLAMF9 下调。此外，PAE 抑制 M1 巨噬细胞极化并增强人脐静脉内皮细胞（HUVEC）的增殖、迁移和血管生成。当过表达 LINC01133 或 SLAMF9 时，这些作用会减弱。从机制上讲，LINC01133 通过与 ELAVL1 相互作用而上调 SLAMF9。SLAMF9 的过表达逆转了 LINC01133 沉默对巨噬细胞极化和 HUVEC 功能的影响。总之，PAE 通过下调 LINC01133/SLAMF9 通路促进感染性糖尿病性溃疡的愈合。
