Yadu Nidhi, Singh Manju, Singh Deependra, Keshavkant S
School of Studies in Biotechnology, Pt. Ravishankar Shukla University, Raipur 492 010, India.
University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur 492 010, India.
Int J Pharm. 2025 Feb 10;670:125117. doi: 10.1016/j.ijpharm.2024.125117. Epub 2024 Dec 22.
Wounds that represent one of the most critical complications can occur in individuals suffering from diabetes mellitus, and results in the need for hospitalisation and, in severe cases, require amputation. This condition is primarily characterized by infections, persistent inflammation, and delayed healing processes, which exacerbate the overall health of the patients. As per the standard mechanism, signalling pathways such as PI3K/AKT, HIF-1, TGF-β, Notch, Wnt/β-Cat, NF-κB, JAK/STAT, TLR, and Nrf2 play major roles in inflammatory, proliferative and remodelling phases of wound healing. However, dysregulation of the above pathways has been seen during the healing of diabetic wounds. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the expression of various genes and signalling pathways which are associated with the process of wound healing. In the past few years, there has been a great deal of interest in the potential of miRNAs as biological agents in the management of a number of disorders. These miRNAs have been shown to modulate expression of genes involved in the healing process of wounds. There have been previous reviews pertaining to clinical trials examining miRNAs in several disorders, but only a few clinical studies have examined involvement of miRNAs in healing of wounds. Considering the therapeutic promise, there are several obstacles concerning their instabilities and inefficient delivery into the target cells. Therefore, this review is an attempt to discuss precise roles of signalling pathways and miRNAs in different phases of wound healing, and their aberrant regulation in diabetic wounds, particularly. It has also compiled a range of delivery mechanisms as well as an overview of the latest findings pertaining to miRNAs and associated delivery systems for improved healing of diabetic wounds.
糖尿病患者可能会出现伤口，这是最严重的并发症之一，会导致患者需要住院治疗，严重时还需要截肢。这种情况主要表现为感染、持续炎症和愈合过程延迟，这些都会加重患者的整体健康问题。按照标准机制，PI3K/AKT、HIF-1、TGF-β、Notch、Wnt/β-Cat、NF-κB、JAK/STAT、TLR和Nrf2等信号通路在伤口愈合的炎症、增殖和重塑阶段发挥主要作用。然而，在糖尿病伤口愈合过程中，上述信号通路出现了失调。微小RNA（miRNA）是小的非编码RNA，可调节与伤口愈合过程相关的各种基因和信号通路的表达。在过去几年中，人们对miRNA作为生物制剂治疗多种疾病的潜力产生了浓厚兴趣。这些miRNA已被证明可调节参与伤口愈合过程的基因表达。此前已有关于在多种疾病中研究miRNA的临床试验的综述，但只有少数临床研究探讨了miRNA在伤口愈合中的作用。考虑到其治疗前景，miRNA存在一些问题，比如稳定性差以及难以有效递送至靶细胞。因此，本综述旨在探讨信号通路和miRNA在伤口愈合不同阶段的具体作用，尤其是它们在糖尿病伤口中的异常调控。本综述还汇总了一系列递送机制，并概述了有关miRNA和相关递送系统以促进糖尿病伤口愈合的最新研究成果。
