免疫组织化学
免疫沉淀
体内
发病机制
伤口愈合
医学
癌症研究
细胞生物学
糖尿病
病理
炎症
免疫学
生物
内分泌学
抗体
生物技术
作者
Le Kuai,Yan-Wei Xiang,Qilong Chen,Yi Ru,Yin Su,Wei Li,Jingsi Jiang,Ying Luo,Jiankun Song,Bei Lü,Yue Luo,Bin Li
标识
DOI:10.1016/j.jid.2021.06.028
摘要
Persistent chronic inflammation and delayed epithelialization lead to stalled healing in diabetic ulcers (DUs). PD-L1 shows anti-inflammatory and proliferative activities in healing defects, whereas its function in DU pathogenesis remains unknown. Lower levels of PD-L1 were found in DU tissues, and exogenous PD-L1 has therapeutic effects in the healing process by accelerating re-epithelialization and attenuating prolonged inflammation, which contributed to the delayed wound closure. We detected the downstream effectors of PD-L1 using transcriptional profiles and screened the interacting proteins using immunoprecipitation in combination with mass spectrometry and coimmunoprecipitation assays. The biological functions of eIF3I‒PD-L1‒IRS4 axis were tested both in vivo and in vitro. Finally, we validated the expression levels of eIF3I, PD-L1, and IRS4 in DU tissues from human clinical samples by immunohistochemistry staining. Mechanistically, PD-L1 binds to eIF3I and promotes cutaneous diabetic wound healing by downregulating IRS4. These findings identify that the eIF3I‒PD-L1‒IRS4 axis contributes to wound healing defects, which can serve as a potential therapeutic target in DUs.
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