{Reference Type}: Journal Article
{Title}: Restoring Prohealing/Remodeling-Associated M2a/c Macrophages Using ON101 Accelerates Diabetic Wound Healing.
{Author}: Lin CW;Chen CC;Huang WY;Chen YY;Chen ST;Chou HW;Hung CM;Chen WJ;Lu CS;Nian SX;Chen SG;Chang HW;Chang VHS;Liu LY;Kuo ML;Chang SC;Lin CW;Chen CC;Huang WY;Chen YY;Chen ST;Chou HW;Hung CM;Chen WJ;Lu CS;Nian SX;Chen SG;Chang HW;Chang VHS;Liu LY;Kuo ML;Chang SC;
{Journal}: JID Innov
{Volume}: 2
{Issue}: 5
{Year}: Sep 2022
暂无{DOI}: 10.1016/j.xjidi.2022.100138
{Abstract}: 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 GCSF and CXCL3 genes 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.