C1q tumor necrosis factor associated protein 3 protects HaCaT via phosphoinositide 3-kinase/protein kinase B activation by PTEN reduction

BACKGROUND Delayed wound repair is commonly observed among individuals with diabetes. AIM To determine the mechanism of C1q tumor necrosis factor associated protein 3 (CTRP3) in regulation of wound healing. METHODS Wounds were created in wild-type C57BL/6J and db/db diabetic mice. CTRP3 expression was measured in mouse blood on days 0, 4, 8, 12, 16 and in high glucose-treated HaCaT cells. CTRP3’s role was assessed via cell growth and migration assays. Vascular endothelial growth factor (VEGF) levels were detected. A phospho-kinase array identified phosphorylated kinases. Co-immunoprecipitation verified CTRP3 interaction with phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway proteins. RESULTS CTRP3 expression increased significantly with the passage of wound healing time and CTRP3 expression is low in high-glucose-treated HaCaT cells. High glucose treatment significantly suppressed the cell growth and migration of HaCaT cells, while high expression of CTRP3 reversed the effects of high glucose. Meanwhile, the growth factor VEGF down-regulated by high glucose treatment in HaCaT cells significantly elevated in HaCaT cells with highly-expressed CTRP3. CTRP3 promotes wound healing in diabetic mice in vivo . Moreover, CTRP3 activates PI3K/AKT pathway by reducing PTEN protein level. CONCLUSION CTRP3 accelerates diabetic wound healing, potentially by protecting keratinocytes through downregulating PTEN and activating the PI3K/AKT pathway, presenting a novel therapeutic target.