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

IF 4 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Chinese Journal of Natural Medicines Pub Date : 2024-07-01 DOI:10.1016/S1875-5364(24)60569-8
YANG Yuhang , HUANG Jun , LI Xintian , LIN Renjing , WANG Xiaoyan , XIAO Ge , ZENG Juanni , WANG Zhenquan
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Abstract

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.

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美洲长春花提取物通过下调 LINC01133/SLAMF9 促进感染性糖尿病溃疡伤口愈合
糖尿病溃疡的伤口愈合仍然是一项重大的临床挑战,主要原因是细菌感染和血管生成受损。美洲长春花提取物(PAE)已被广泛用于治疗糖尿病伤口,但其潜在机制尚未完全明了。本研究旨在利用高通量测序技术分析糖尿病肛瘘患者伤口组织中长非编码RNA(lncRNA)的表达,从而阐明这些机制。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,在接受 PAE 治疗的患者伤口组织中,LINC01133 和 SLAMF9 被下调。此外,PAE抑制了M1巨噬细胞的极化,并增强了人脐静脉内皮细胞(HUVEC)的增殖、迁移和血管生成。当过量表达 LINC01133 或 SLAMF9 时,这些作用会减弱。从机理上讲,LINC01133 是通过与 ELAVL1 相互作用来上调 SLAMF9 的。过表达 SLAMF9 逆转了 LINC01133 沉默对巨噬细胞极化和 HUVEC 功能的影响。总之,PAE 可通过下调 LINC01133/SLAMF9 通路促进感染性糖尿病溃疡的愈合。
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来源期刊
Chinese Journal of Natural Medicines
Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.50
自引率
4.30%
发文量
2235
期刊介绍: The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.
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