Vascular calcification (VC), which is associated with high cardiovascular morbidity and mortality in patients with chronic kidney disease, is promoted by the osteoblastic differentiation of vascular smooth muscle cells (VSMCs). The present study explored the functional roles and molecular mechanisms of the long noncoding RNA growth arrest-specific transcript 5 (GAS5) in VC. Our results indicated that GAS5 was clearly downregulated in calcified human aortic vascular smooth muscle cells (HASMCs). Functionally, we found that overexpression of GAS5 significantly attenuated the osteogenic differentiation and calcification of HASMCs induced by high levels of phosphorus. Moreover, miR-26-5p was identified to potentially bind to GAS5, and phosphatase and tensin homolog (PTEN) was determined to be a direct target of miR-26b-5p in HASMCs. Mechanistically, enforced expression of miR-26-5p significantly attenuated PTEN protein expression in HASMCs. Rescue experiments demonstrated that cotransfection of HASMCs with miR-26-5p mimics reduced the inhibition of Lv-GAS5 on osteogenic differentiation and calcification. As a result, GAS5 was confirmed to be an miR-26b-5p sponge and to thereby increase the expression of PTEN in HASMCs. In ex vivo models, GAS5 was significantly downregulated and its expression inversely related to the expression of miR-26b-5 and positively associated with the expression of PTEN in calcified aortic rings induced by high levels of phosphorus. Together, these results suggest that the GAS5/miR-26-5p/PTEN axis could serve as a potential therapeutic target for VC in patients with chronic kidney disease.

血管钙化（VC）与慢性肾脏病患者的高心血管疾病发病率和死亡率有关，是由血管平滑肌细胞（VSMC）的成骨细胞分化促进的。本研究探讨了VC中长的非编码RNA生长停滞特异性转录本5（GAS5）的功能作用和分子机制。我们的结果表明，GAS5在钙化的人主动脉血管平滑肌细胞（HASMC）中明显下调。在功能上，我们发现GAS5的过表达显着减弱了高磷诱导的HASMC的成骨分化和钙化。此外，已确定miR-26-5p可能与GAS5结合，并且已确定磷酸酶和张力蛋白同源物（PTEN）是HASMC中miR-26b-5p的直接靶标。机械上，miR-26-5p的强制表达可显着减弱HASMC中PTEN蛋白的表达。救援实验表明HASMC与miR-26-5p模拟物的共转染可降低Lv-GAS5对成骨细胞分化和钙化的抑制作用。结果，证实GAS5是miR-26b-5p海绵，从而增加了HASMC中PTEN的表达。在离体模型中，GAS5显着下调，其表达与miR-26b-5的表达呈负相关，与高磷诱导的钙化主动脉环中PTEN的表达呈正相关。总之，这些结果表明，GAS5 / miR-26-5p / PTEN轴可作为慢性肾脏病患者VC的潜在治疗靶标。