Li Tao, Ma Yu, Wang Min, Wang Tao, Wei Jing, Ren Rui, He Min, Wang Guixue, Boey Johnson, Armstrong David G, Deng Wuquan, Chen Bing
Department of Endocrinology, Southwest Hospital, Army Medical University, Chongqing, People's Republic of China,
Department of Endocrinology and Nephrology, Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Affiliated Central Hospital of Chongqing University, Chongqing, People's Republic of China,
Infect Drug Resist. 2019 Jan 29;12:297-309. doi: 10.2147/IDR.S186651. eCollection 2019.
This study was designed to examine the potential mechanism underlying these roles of platelet-rich plasma in treating diabetic foot ulcers (DFUs).
and HaCaT were co-cultured under high glucose conditions to serve as an in vitro model for infected cells in DFUs. Platelet-rich gel (PRG) or extract liquid of platelet-rich gel (EPG) were used to interfere with the model to observe the growth of HaCaT cells and , and the effect of miR-21 changes in HaCaT cells on PDCD4, NF-κB activity and related inflammatory factors.
Incubation of HaCaT cells with promoted the decline of cell proliferation. Under this condition, the level of PDCD4 and the activity of NF-κB were increased in HaCaT cells with concomitant increased of IL-6, TNF-α and decreased IL-10, TGF-β1 in cultured supernatant. Both of PRG and EPG exhibited specific anti- activity where they protect HaCaT cells from bacterial damage and promote cell proliferation. Meanwhile, EPG was observed to increase intracellular miRNA-21 while reduce PDCD4 expression and inhibit NF-κB activity to suppress the inflammation in HaCaT cells.
This in vitro model provides a valuable tool for study of wound healing in the treatment of DFUs. Our results suggest that miRNA-21 may regulate the expression of NF-κB through PDCD4 where it plays an anti-inflammatory role and promote proliferation in infected DFUs treated by PRP. These findings could provide novel therapeutic targets for refractory wounds.
本研究旨在探讨富血小板血浆治疗糖尿病足溃疡（DFUs）这些作用的潜在机制。
将HaCaT细胞在高糖条件下共培养，作为DFUs感染细胞的体外模型。使用富血小板凝胶（PRG）或富血小板凝胶提取液（EPG）干预该模型，观察HaCaT细胞的生长情况，以及HaCaT细胞中miR-21变化对程序性细胞死亡蛋白4（PDCD4）、核因子κB（NF-κB）活性和相关炎症因子的影响。
用 培养HaCaT细胞促进了细胞增殖的下降。在此条件下，HaCaT细胞中PDCD4水平和NF-κB活性增加，同时培养上清液中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）增加，白细胞介素-10（IL-10）、转化生长因子-β1（TGF-β1）减少。PRG和EPG均表现出特异性的抗 活性，它们保护HaCaT细胞免受细菌损伤并促进细胞增殖。同时，观察到EPG增加细胞内微小RNA-21（miRNA-21），同时降低PDCD4表达并抑制NF-κB活性，以抑制HaCaT细胞中的炎症。
该体外模型为研究DFUs治疗中的伤口愈合提供了有价值的工具。我们的结果表明，miRNA-21可能通过PDCD4调节NF-κB的表达，在富血小板血浆（PRP）治疗的感染性DFUs中发挥抗炎作用并促进增殖。这些发现可为难治性伤口提供新的治疗靶点。
