Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing endogenous RNA for the treatment of diabetic wounds

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.

HIF1α overexpression enhances diabetic wound closure in high glucose and low oxygen conditions by promoting adipose-derived stem cell paracrine function and survival

“…Diabetes mellitus is a serious chronic metabolic disorder characterized by high glucose levels, which induces oxidative stress. It affects more than 400 million people worldwide, with a predicted > 50% increase in cases by 2030 [1][2][3]. Micro-and macrovascular diseases are key complications of diabetes and may be important risk factors for death in diabetic patients [4,5].…”

EWSAT1 Acts in Concert with Exosomes in Osteosarcoma Progression and Tumor‐Induced Angiogenesis: The “Double Stacking Effect”

“…[ 5a,21 ] The HMEC1 cells were cultured per our published method. [ 5a,19d,22 ] All cell lines were verified to be Mycoplasma‐free using a Venor GeM Mycoplasma detection kit (Sigma‐Aldrich, USA). All cells were cultured in the presence of 5% CO 2 at 37 °C.…”

“…Specific experimental procedures and methods were described in detail in our previous studies. [ 17a,19b,d,22b,32 ]…”

Expedition to the missing link: Long noncoding RNAs in cardiovascular diseases

“…Interestingly, even though its expression was only retained in a few adult tissues, H19 was found to be involved in the dysregulation of ECs during atherosclerosis. Hyperglycemia leads to H19 downregulation in ECs, which is linked to impaired angiogenesis [80], strongly suggesting the critical role of H19 in the pathogenesis of atherosclerosis. MALAT1 is a conserved lncRNA ubiquitously expressed in a number of cells and tissues, and can be induced in response to many pathological stimulations including hypoxia, high glucose and oxidative stress.…”