Abstract
Diabetic wounds, one of the most enervating complications of diabetes mellitus, affect millions of people worldwide annually. Vascular insufficiency, caused by hyperglycemia, is one of the primary causes and categories of diabetic impaired wound healing. Recently, long noncoding RNA (LncRNA)-H19, which is significantly decreased in diabetes and may be crucial in triggering angiogenesis, has attracted increasing interest. The possible relationship between the decrease of LncRNA-H19 and the impairment of angiogenesis in diabetes could involve impairment of the insulin–phosphatidylinositol 3-kinase (PI3K)–Akt pathway via the interdiction of LncRNA-H19. Thus, a therapeutic strategy utilizing LncRNA-H19 delivery is feasible. In this study, we investigated the possibility of using high-yield extracellular vesicle-mimetic nanovesicles (EMNVs) as an effective nano-drug delivery system for LncRNA, and studied the function of EMNVs with a high content of LncRNA-H19 (H19EMNVs). The results, which were exciting, showed that H19EMNVs had a strong ability to neutralize the regeneration-inhibiting effect of hyperglycemia, and could remarkably accelerate the healing processes of chronic wounds. Our results suggest that bioengineered EMNVs can serve as a powerful instrument to effectively deliver LncRNA and will be an extremely promising multifunctional drug delivery system in the immediate future.
Highlights
Diabetic chronic wounds, one of the most enervating complications of diabetes mellitus (Tao et al, 2017a), are defined as barrier defects that have not proceeded through orderly and timely repair to regain structural and functional integrity (Bergan et al, 2006)
The extracellular vesicle-mimetic nanovesicles (EMNVs) derived from HEK-293 cells transfected by empty vector (293EMNVs) and stable H19-highexpressing human embryonic kidney cells 293 (HEK293) cells (H19EMNVs) were prepared and purified following the procedure described in the “Methods” section
Western blotting showed the presence of exosome markers, such as CD9, CD63, and CD81 (Figure 1(d)), which further confirmed the similarities between extracellular vesicles and EMNVs
Summary
One of the most enervating complications of diabetes mellitus (Tao et al, 2017a), are defined as barrier defects that have not proceeded through orderly and timely repair to regain structural and functional integrity (Bergan et al, 2006). Vascular insufficiency is one of the primary causes and categories of chronic non-healing cutaneous wounds, systemic factors, including compromised nutritional or immunological status, advanced age, chronic mechanical stress, and other comorbidities, contribute to poor wound healing (Morton & Phillips, 2016). Poor wound healing affects millions of people worldwide each year and is the consequence of poorly-regulated elements of the healthy tissue repair response, especially angiogenesis (Ruttermann et al, 2013). Competing endogenous RNAs (ceRNAs) are transcripts, including messenger RNAs (mRNAs), long non-coding RNAs (LncRNAs) and circular RNAs (circRNAs), which regulate each other by competitive binding to shared microRNAs (miRNAs) (Salmena et al, 2011). Accumulating evidence indicates that LncRNAs could contain miRNA-response elements (MRE), which could compete with mRNAs as ceRNAs (Cesana et al, 2011)
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