Bastaki Khaled Mahmoud, Tarlton Jamie Maurice Roy, Lightbody Richard James, Graham Annette, Martin Patricia Esther
Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK.
Membranes (Basel). 2022 Jan 27;12(2):154. doi: 10.3390/membranes12020154.
Chronic, non-healing wounds are a significant cause of global morbidity and mortality, and strategies to improve delayed wound closure represent an unmet clinical need. High-density lipoproteins (HDL) can enhance wound healing, but exploitation of this finding is challenging due to the complexity and instability of these heterogeneous lipoproteins. The responsiveness of primary human neonatal keratinocytes, and neonatal and human dermal fibroblasts (HDF) to HDL was confirmed by cholesterol efflux, but promotion of 'scrape' wound healing occurred only in primary human neonatal (HDFn) and adult fibroblasts (HDFa). Treatment of human fibroblasts with HDL induced multiple changes in the expression of small non-coding microRNA sequences, determined by microchip array, including hsa-miR-6727-5p. Intriguingly, levels of hsa-miR-6727-5p increased in HDFn, but decreased in HDFa, after exposure to HDL. Delivery of a hsa-miR-6727-5p mimic elicited repression of different target genes in HDFn () and HDFa (, ), and promoted wound closure in HDFn. By contrast, a hsa-miR-6727-5p inhibitor promoted wound closure in HDFa. We conclude that HDL treatment exerts distinct effects on the expression of hsa-miR-6727-5p in neonatal and adult fibroblasts, and that this is a sequence which plays differential roles in wound healing in these cell types, but cannot replicate the myriad effects of HDL.
慢性难愈合伤口是全球发病率和死亡率的一个重要原因，改善伤口延迟愈合的策略是一项尚未满足的临床需求。高密度脂蛋白（HDL）可以促进伤口愈合，但由于这些异质性脂蛋白的复杂性和不稳定性，利用这一发现具有挑战性。通过胆固醇外流证实了原代人新生儿角质形成细胞、新生儿和人真皮成纤维细胞（HDF）对HDL的反应性，但“刮擦”伤口愈合的促进仅发生在原代人新生儿（HDFn）和成人成纤维细胞（HDFa）中。用HDL处理人成纤维细胞会诱导小非编码微小RNA序列表达的多种变化，通过微芯片阵列确定，包括hsa-miR-6727-5p。有趣的是，暴露于HDL后，HDFn中hsa-miR-6727-5p的水平升高，而HDFa中则降低。递送hsa-miR-6727-5p模拟物会在HDFn（）和HDFa（，）中引发不同靶基因的抑制，并促进HDFn中的伤口闭合。相比之下，hsa-miR-6727-5p抑制剂促进了HDFa中的伤口闭合。我们得出结论，HDL处理对新生儿和成纤维细胞中hsa-miR-6727-5p的表达产生不同影响，并且这是一个在这些细胞类型的伤口愈合中发挥不同作用的序列，但不能复制HDL的众多作用。
