Department of Dermatology, The Second Hospital of Dalian Medical University, College of Integrative Medicine, Dalian Medical University, Dalian, China.
Dermatology and Venereology Unit, Department of Medicine (Solna), Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Adv Wound Care (New Rochelle). 2020 Apr 1;9(4):145-160. doi: 10.1089/wound.2019.0956. Epub 2020 Feb 7.
Insufficient knowledge about the molecular pathology of diabetic foot ulcer (DFU) impedes the development of effective wound treatment. Circular RNAs (circRNAs) are a novel class of RNA recently discovered to be widely expressed and have important biological functions; however, their role in skin wound healing remains largely unexplored. In this study, we investigated the role of circRNAs in DFU. CircRNA expression was profiled in normal wounds (NWs) and DFUs by microarray analysis, and hsa_circ_0084443 was identified as differentially expressed. The circularity and subcellular localization of hsa_circ_0084443 were characterized by northern blotting, real-time PCR, and fluorescence hybridization. Cell migration, cell growth, and the transcriptome of human primary keratinocytes were analyzed after overexpression or RNA interference of hsa_circ_0084443. hsa_circ_0084443 is downregulated in NWs compared with intact skin, and its level is higher in DFUs than NWs. We confirmed its circularity and presence in the cytoplasm of human epidermal keratinocytes. We showed that hsa_circ_0084443 reduced motility while enhancing the growth of keratinocytes. Furthermore, we identified a gene network with the potential to mediate the biological effect of hsa_circ_0084443. CircRNAs have a functional role and a potential clinical significance in skin wound healing. We identified hsa_circ_0084443, a circRNA downregulated during NW healing, as a negative regulator of keratinocyte migration. Higher levels of hsa_circ_0084443 were detected in DFU samples, suggesting that it plays a role in pathology. These findings pave the way to understanding the functional role of circRNAs in human skin wound healing.
关于糖尿病足溃疡 (DFU) 的分子病理学的知识不足，阻碍了有效的伤口治疗的发展。环状 RNA (circRNA) 是一类新发现的 RNA，广泛表达并具有重要的生物学功能；然而，它们在皮肤伤口愈合中的作用在很大程度上仍未被探索。在这项研究中，我们研究了 circRNA 在 DFU 中的作用。通过微阵列分析对正常伤口 (NWs) 和 DFUs 中的 circRNA 表达进行了分析，并确定 hsa_circ_0084443 为差异表达。通过Northern blot、实时 PCR 和荧光杂交鉴定 hsa_circ_0084443 的圆性和亚细胞定位。过表达或 RNA 干扰 hsa_circ_0084443 后，分析人原代角质形成细胞的细胞迁移、细胞生长和转录组。与完整皮肤相比，hsa_circ_0084443 在 NWs 中下调，在 DFUs 中高于 NWs。我们证实了其在人表皮角质形成细胞中的圆性和存在于细胞质中。我们表明 hsa_circ_0084443 降低了运动能力，同时增强了角质形成细胞的生长。此外，我们鉴定了一个具有潜在能力的基因网络，以介导 hsa_circ_0084443 的生物学效应。环状 RNA 在皮肤伤口愈合中具有功能作用和潜在的临床意义。我们鉴定了 hsa_circ_0084443，一种在 NW 愈合过程中下调的 circRNA，作为角质形成细胞迁移的负调节剂。在 DFU 样本中检测到更高水平的 hsa_circ_0084443，表明其在发病机制中发挥作用。这些发现为理解 circRNA 在人类皮肤伤口愈合中的功能作用铺平了道路。
