Abstract
Numerous studies have reported that autophagy plays an important role in chronic wound healing, and enhancement of autophagic activity impairs cutaneous wound healing. The autophagy inhibitor Bafilomycin A1 (Baf A1) inhibits autophagy by preventing the formation of autophagosomes. This study aimed at elucidating the effect of Bafilomycin A1 on chronic refractory wound healing in diabetic mice. A total of 40 diabetic (db/db) mice and 20 nondiabetic (db/m) mice were used in this study. Full-thickness skin defects were generated in the db/db mice models, which were then divided into the following two groups: the nontreated (db/db group) and Baf A1-treated groups (Baf A1 group). The same skin defects were generated in db/m mice (db/m group) to serve as a control. We demonstrated that Baf A1 treatment significantly accelerated wound healing in db/db mice and exerted good healing effects. Moreover, Baf A1 inhibited autophagy in the newly generated epidermis and had minor effects on metabolism in db/db mice. PCNA expression, as detected by immunohistochemistry, and collagen thickness, as detected by Masson's trichrome staining on the 14th day, were higher in the db/m and Baf A1 groups than in the db/db group. In addition, the expression of the proinflammatory cytokine TNF-α in the db/m and Baf A1 groups increased significantly on day 6, and the expression of the anti-inflammatory cytokine IL-10 also increased significantly on day 9. However, there were no significant changes in the expression levels of TNF-α and IL-10 in the db/db group. Therefore, Baf A1 may accelerate diabetic chronic refractory wound healing by promoting cell proliferation, collagen production, and regulating the inflammatory balance.
Highlights
Wound healing is a complex and dynamic process that is affected by many factors
We evaluated the effects of the autophagy inducer rapamycin and autophagy inhibitor Bafilomycin A1 (Baf A1) on chronic refractory wound healing in hyperglycemic mice; data showed that rapamycin delayed wound healing which is consistent with previous description, whereas Baf A1 accelerates wound healing comparing with the control
To investigate the underlying mechanism, we evaluated the effect of Baf A1 on cell proliferation, collagen production, and inflammatory cytokine secretion during wound healing to assess the relationship between autophagy and wound healing
Summary
Wound healing is a complex and dynamic process that is affected by many factors. Chronic refractory wounds can be caused by numerous conditions, such as advanced age, poor nutrition, infection, stress, and medication [1,2,3]. Diabetes mellitus (DM) is one of the most common factors causing chronic wounds, and delayed wound healing is one of the most serious complications of diabetes [4]. Despite considerable studies on the pathogenesis of delayed wound healing caused by diabetes, the underlying molecular mechanisms are poorly understood. Increasing evidence has implicated autophagic dysfunction in the development of neurodegenerative diseases, cancer, infection, and aging [10], and some studies have linked autophagic activity and its regulation with wound healing. A study conducted by Guo et al showed
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