Department of Ophthalmology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan, China.
Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan, China.
Aging (Albany NY). 2020 May 26;12(10):9085-9102. doi: 10.18632/aging.103176.
Pulmonary fibrosis (PF) is a lethal fibrotic lung disease. The role of lncRNAs in multiple diseases has been confirmed, but the role and mechanism of lncRNA zinc finger antisense 1 (ZFAS1) in the progression of PF need to be elucidated further. Here, we found that lncRNA ZFAS1 was upregulated in bleomycin (BLM)-induced PF rats lung tissues and transforming growth factor-β1 (TGF-β1)-treated HFL1 cells, and positively correlated with the expression of solute carrier family 38 member 1 (SLC38A1), which is an important regulator of lipid peroxidation. Moreover, knockdown of lncRNA ZFAS1 significantly alleviated TGF-β1-induced fibroblast activation, inflammation and lipid peroxidation. experiments showed that inhibition of lncRNA ZFAS1 abolished BLM-induced lipid peroxidation and PF development. Mechanistically, silencing of lncRNA ZFAS1 attenuated ferroptosis and PF progression by lncRNA ZFAS1 acting as a competing endogenous RNA (ceRNA) and sponging miR-150-5p to downregulate SLC38A1 expression. Collectively, our studies demonstrated the role of the lncRNA ZFAS1/miR-150-5p/SLC38A1 axis in the progression of PF, and may provide a new biomarker for the treatment of PF patients.
肺纤维化（PF）是一种致命的肺纤维化疾病。lncRNAs 在多种疾病中的作用已得到证实，但 lncRNA 锌指反义 1（ZFAS1）在 PF 进展中的作用和机制仍需进一步阐明。在这里，我们发现 lncRNA ZFAS1 在博来霉素（BLM）诱导的 PF 大鼠肺组织和转化生长因子-β1（TGF-β1）处理的 HFL1 细胞中上调，并且与溶质载体家族 38 成员 1（SLC38A1）的表达呈正相关，SLC38A1 是脂质过氧化的重要调节因子。此外，lncRNA ZFAS1 的敲低显着减轻了 TGF-β1 诱导的成纤维细胞活化、炎症和脂质过氧化。实验表明，抑制 lncRNA ZFAS1 可消除 BLM 诱导的脂质过氧化和 PF 发展。机制上，lncRNA ZFAS1 通过作为竞争性内源性 RNA（ceRNA）并吸收 miR-150-5p 来下调 SLC38A1 表达，从而减弱 ferroptosis 和 PF 进展。总之，我们的研究表明 lncRNA ZFAS1/miR-150-5p/SLC38A1 轴在 PF 进展中的作用，并可为 PF 患者的治疗提供新的生物标志物。
