Restoring Prohealing/Remodeling-Associated M2a/c Macrophages Using ON101 Accelerates Diabetic Wound Healing

التفاصيل البيبلوغرافية
العنوان: Restoring Prohealing/Remodeling-Associated M2a/c Macrophages Using ON101 Accelerates Diabetic Wound Healing
المؤلفون: Lin, Ching-Wen, Chen, Chih-Chiang, Huang, Wen-Yen, Chen, Yen-Yu, Chen, Shiou-Ting, Chou, Hung-Wen, Hung, Chien-Ming, Chen, Wan-Jiun, Lu, Chia-Sing, Nian, Shi-Xin, Chen, Shyi-Gen, Chang, Hsuen-Wen, Chang, Vincent H.S., Liu, Li-Ying, Kuo, Ming-Liang, Chang, Shun-Cheng
المصدر: JID Innovations; September 2022, Vol. 2 Issue: 5
مستخلص: Diabetic wounds exhibit chronic inflammation and delayed tissue proliferation or remodeling, mainly owing to prolonged proinflammatory (M1) macrophage activity and defects in transition to prohealing/proremodeling (M2a/M2c; CD206+and/or CD163+) macrophages. We found that topical treatment with ON101, a plant-based potential therapeutic for diabetic foot ulcers, increased M2c-like (CD163+and CD206+) cells and suppressed M1-like cells, altering the inflammatory gene profile in a diabetic mouse model compared with that in the controls. An in vitro macrophage-polarizing model revealed that ON101 directly suppressed CD80+and CD86+M1-macrophage polarization and M1-associated proinflammatory cytokines at both protein and transcriptional levels. Notably, conditioned medium collected from ON101-treated M1 macrophages reversed the M1-conditioned medium‒mediated suppression of CD206+macrophages. Furthermore, conditioned medium from ON101-treated adipocyte progenitor cells significantly promoted CD206+and CD163+macrophages but strongly inhibited M1-like cells. ON101 treatment also stimulated the expression of GCSFand CXCL3genes in human adipocyte progenitor cells. Interestingly, treatment with recombinant GCSF protein enhanced both CD206+and CD163+M2 markers, whereas CXCL3 treatment only stimulated CD163+M2 macrophages. Depletion of cutaneous M2 macrophages inhibited ON101-induced diabetic wound healing. Thus, ON101 directly suppressed M1 macrophages and facilitated the GCSF- and CXCL3-mediated transition from M1 to M2 macrophages, lowering inflammation and leading to faster diabetic wound healing.
قاعدة البيانات: Supplemental Index
الوصف
تدمد:26670267
DOI:10.1016/j.xjidi.2022.100138