DPP-4 Inhibitors Improve Diabetic Wound Healing via Direct and Indirect Promotion of Epithelial-Mesenchymal Transition and Reduction of Scarring

被引：89

作者：

Long, Min ^{[1
]}

Cai, Leiqin ^{[1
]}

Li, Wenjie ^{[1
]}

Zhang, Linlin ^{[1
]}

Guo, Shaodong ^{[2
]}

Zhang, Rui ^{[1
]}

Zheng, Yi ^{[1
]}

Liu, Xiufei ^{[1
]}

Wang, Min ^{[1
]}

Zhou, Xianli ^{[1
]}

Wang, Hui ^{[1
]}

Li, Xing ^{[1
]}

Li, Ling ^{[3
]}

Zhu, Zhiming ^{[4
]}

Yang, Gangyi ^{[5
]}

Zheng, Hongting ^{[1
]}

机构：

[1] Third Mil Med Univ, Xinqiao Hosp, Translat Res Key Lab Diabet, Dept Endocrinol, Chongqing, Peoples R China

[2] Texas A&M Univ, Coll Agr & Life Sci, Dept Nutr & Food Sci, College Stn, TX USA

[3] Chongqing Med Univ, Coll Lab Med, Dept Clin Biochem, Chongqing, Peoples R China

[4] Third Mil Med Univ, Daping Hosp, Dept Hypertens & Endocrinol, Chongqing, Peoples R China

[5] Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Chongqing, Peoples R China

来源：

DIABETES | 2018年 / 67卷 / 03期

基金：

中国国家自然科学基金;

关键词：

COLLECTIVE MIGRATION; LEADER CELLS; DOUBLE-BLIND; SKIN; NRF2; STREPTOZOTOCIN; PLACEBO; GROWTH; MICE; IV;

D O I：

10.2337/db17-0934

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Patients with diabetes often experience multiple disease complications. Hypoglycemic agents can have both positive and negative effects on diabetic complications, which should be carefully assessed when personalized treatment strategies are developed. In this study we report that dipeptidyl peptidase 4 inhibitors ( DPP-4is), a group of widely used antihyperglycemic agents, can improve diabetic wound healing, independent of their beneficial effects on glycemic control. In particular, DPP-4is promoted the migration and epithelial-mesenchymal transition of keratinocytes, directly and indirectly, by inducing stromal cell-derived factor 1 alpha production of fibroblasts in vitro and in diabetic mice. In addition, DPP-4is attenuated collagen synthesis and deposition, which may diminish scar formation. Furthermore, the results of a randomized clinical trial ( NCT02742233) involving 67 patients with type 2 diabetes supported the role of DPP-4i treatment in diabetic wound healing. Our findings support the application of DPP-4i as a preferred option for treating ulcers in patients with diabetes.

引用

页码：518 / 531

页数：14

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