Sakshi Shukla, Jayasuriya Ravichandran, Sathish Kumar Rajappan Chandra, Umapathy Dhamodharan, Gopinathan Athira, Balamurugan Ramachandran, Ganesan Kumar, Ramkumar Kunka Mohanram
Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
Interdisciplinary Institute of Indian System and Medicine (IIISM), SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
J Clin Med. 2023 Jul 7;12(13):4551. doi: 10.3390/jcm12134551.
Nuclear factor erythroid-2-related factor 2 () is a stress-activated transcription factor regulating antioxidant genes, and a deficiency thereof, slowing lymphangiogenesis, has been reported in diabetic foot ulcer (DFU). The mode of regulation in DFU has been less explored. Emerging studies on miRNA-mediated target regulation show miRNA to be the leading player in the pathogenesis of the disease. In the present study, we demonstrated the role of miR-27b in regulating -mediated angiogenesis in DFU. A lower expression of mRNA targets, such as , , , and , was observed in tissue biopsied from chronic DFU subjects, which was in line with miR-27b, signifying a positive correlation with . Similarly, we found significantly reduced expression of miR-27b and target mRNAs , , , and in endothelial cells under a hyperglycemic microenvironment (HGM). To confirm the association of miR-27b on regulating -mediated angiogenesis, we inhibited its expression through RNA interference-mediated knockdown and observed disturbances in angiogenic signaling with reduced endothelial cell migration. In addition, to explore the role of miR-27b and angiogenesis in the activation of , we pretreated the endothelial cells with two well-known pharmacological compounds-pterostilbene and resveratrol. We observed that activation of through these compounds ameliorates impaired angiogenesis on HGM-induced endothelial cells. This study suggests a positive role of miR-27b in regulating , which seems to be decreased in DFU and improves on treatment with pterostilbene and resveratrol.
核因子红细胞2相关因子2（）是一种应激激活的转录因子，可调节抗氧化基因，据报道，糖尿病足溃疡（DFU）中该因子缺乏会减缓淋巴管生成。DFU中调节的模式尚未得到充分探索。关于miRNA介导的靶标调节的新兴研究表明，miRNA是该疾病发病机制中的主要参与者。在本研究中，我们证明了miR-27b在调节DFU中介导的血管生成中的作用。在慢性DFU患者的组织活检中观察到、、、等mRNA靶标的表达较低，这与miR-27b一致，表明与呈正相关。同样，我们发现在高血糖微环境（HGM）下，内皮细胞中miR-27b和靶标mRNA、、、的表达显著降低。为了证实miR-27b与调节介导的血管生成之间的关联，我们通过RNA干扰介导的敲低抑制其表达，并观察到血管生成信号紊乱，内皮细胞迁移减少。此外，为了探索miR-27b和血管生成在激活中的作用，我们用两种著名的药理化合物——紫檀芪和白藜芦醇预处理内皮细胞。我们观察到通过这些化合物激活可改善HGM诱导的内皮细胞受损的血管生成。这项研究表明miR-27b在调节中具有积极作用，在DFU中其作用似乎降低，而用紫檀芪和白藜芦醇治疗后有所改善。
