PD-L1 Triggered by Binding eIF3I Contributes to the Amelioration of Diabetes-Associated Wound Healing Defects by Regulating IRS4

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:142

Article

Kuai, Le^1,2  Xiang, Yan-Wei^1,3  Chen, Qi-Long^4,5  Ru, Yi^1,2  Yin, Shuang-Yi⁶  Li, Wei⁶  Jiang, Jing-Si^1,2  Luo, Ying^1,2  Song, Jian-Kun^1,5  Lu, Bing^1,3  Luo, Yue^1,5  Li, Bin^1,5 

[1] Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western, Dept Dermatol, Shanghai, Peoples R China

[2] Shanghai Acad Tradit Chinese Med, Inst Dermatol, Shanghai, Peoples R China

[3] Shanghai Univ Tradit Chinese Med, Sch Rehabil Sci, Shanghai, Peoples R China

[4] Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai, Peoples R China

[5] Tongji Univ, Shanghai Skin Dis Hosp, Sch Med, Shanghai, Peoples R China

[6] Henan Univ, Ctr Translat Med, Huaihe Hosp, Kaifeng, Peoples R China

DOI  :  10.1016/j.jid.2021.06.028

来源: Elsevier

【 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.

【 授权许可】

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