肌腱病是一种常见的肌肉骨骼疾病,具有特征性的血管过多。肌腱病中血管生成的机制尚不清楚。本研究旨在探讨miR-148a-3p在肌腱病血管生成中的作用。在这项研究中,我们证明miR-148a-3p在肌腱病组织中表达增加,并与CD34水平呈正相关,CD34是血管生成的特异性标志物.我们确定Krüppel样因子6(KLF6)是肌腱细胞中miR-148a-3p的直接靶基因。此外,使用qRT-PCR和免疫组织化学分析显示肌腱病变组织中KLF6水平降低,与对照组相比。KLF6mRNA与miR-148a-3p呈负相关。然后,我们证实miR-148a-3p可以通过靶向肌腱细胞中的KLF6调节Tsp-4的表达,并且与肌腱病变组织中的Tsp-4水平呈正相关.在肌腱细胞与内皮细胞(EC)的共培养系统中,我们观察到转染Lv-miR-148a-3p显著上调EC血管生成。总之,我们的数据建立了一种新的分子机制,通过该机制,miR-148a-3p上调Tsp-4在肌腱细胞中的表达,从而通过靶向KLF6促进EC血管生成,这可能有助于未来肌腱病的治疗.
Tendinopathy is a common musculoskeletal disorder with characteristic hypervascularity. The mechanism of angiogenesis in tendinopathy remains unclear. The present study aimed to investigate the roles of miR-148a-3p in angiogenesis development of tendinopathy. In this study, we demonstrated that miR-148a-3p expression was increased in tendinopathy tissues and positively correlated with CD34 levels which is a specific marker for angiogenesis. We identified Krüppel-like factor 6 (KLF6) as a direct target gene of miR-148a-3p in tenocytes. Furthermore, reduced levels of KLF6 in tendinopathy tissues was showed using qRT-PCR and immunohistochemical analysis, compared with controls. A negative correlation between the levels of KLF6 mRNA and miR-148a-3p was observed. Then, we verified that miR-148a-3p could regulate Tsp-4 expression by targeting KLF6 in tenocyte and was positively correlated with Tsp-4 levels in tendinopathy tissues. In a coculture system of tenocytes with endothelial cells (ECs), we observed that transfection of Lv-miR-148a-3p markedly upregulated EC angiogenesis. In summary, our data establish a novel molecular mechanism by which miR-148a-3p upregulates Tsp-4 expression in tenocytes to promote EC angiogenesis by targeting KLF6, which could be helpful for the treatment of tendinopathy in the future.