Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University , Zhengzhou , China.
Henan Provincial Key Laboratory of Child Brain Injury , Zhengzhou , China.
Am J Physiol Cell Physiol. 2019 May 1;316(5):C711-C721. doi: 10.1152/ajpcell.00440.2018. Epub 2019 Feb 6.
Accumulating evidence has highlighted the potential of microRNAs (miRs) as biomarkers in various human diseases. However, the roles of miRs in bacterial meningitis (BM), a severe infectious condition, still remain unclear. Thus, the present study aimed to investigate the effects of miR-135a on proliferation and apoptosis of astrocytes in BM. Neonatal rats were injected with to establish the BM model. The expression of miR-135a and hypoxia-inducible factor 1α (HIF-1α) in the BM rat models were characterized, followed by determination of their interaction. Using gain- and loss-of-function approaches, the effects of miR-135a on proliferation, apoptosis, and expression of glial fibrillary acidic protein (GFAP), in addition to apoptosis-related factors in astrocytes were examined accordingly. The regulatory effect of HIF-1α was also determined along with the overexpression or knockdown of HIF-1α. The results obtained indicated that miR-135a was poorly expressed, whereas HIF-1α was highly expressed in the BM rat models. In addition, restored expression levels of miR-135a were determined to promote proliferation while inhibiting the apoptosis of astrocytes, along with downregulated Bax and Bad, as well as upregulated Bcl-2, Bcl-XL, and GFAP. As a target gene of miR-135a, HIF-1α expression was determined to be diminished by miR-135a. The upregulation of HIF-1α reversed the miR-135a-induced proliferation of astrocytes. Taken together, the key findings of the current study present evidence suggesting that miR-135a can downregulate HIF-1α and play a contributory role in the development of astrocytes derived from BM, providing a novel theoretical perspective for BM treatment approaches.
越来越多的证据表明，微小 RNA（miRs）作为各种人类疾病的生物标志物具有潜在作用。然而，miRs 在细菌性脑膜炎（BM）中的作用仍不清楚，BM 是一种严重的感染性疾病。因此，本研究旨在探讨 miR-135a 对 BM 中星形胶质细胞增殖和凋亡的影响。用 建立 BM 大鼠模型，对 BM 大鼠模型中 miR-135a 和缺氧诱导因子 1α（HIF-1α）的表达进行了特征分析，并测定了它们之间的相互作用。采用增益和缺失功能的方法，研究了 miR-135a 对星形胶质细胞增殖、凋亡和胶质纤维酸性蛋白（GFAP）表达以及凋亡相关因子的影响。还测定了 HIF-1α 的调节作用以及 HIF-1α 的过表达或敲低。结果表明，miR-135a 在 BM 大鼠模型中表达水平较低，而 HIF-1α 表达水平较高。此外，恢复 miR-135a 的表达水平可促进星形胶质细胞的增殖，抑制其凋亡，同时下调 Bax 和 Bad，上调 Bcl-2、Bcl-XL 和 GFAP。作为 miR-135a 的靶基因，HIF-1α 的表达被 miR-135a 下调。HIF-1α 的上调逆转了 miR-135a 诱导的星形胶质细胞增殖。综上所述，本研究的主要发现表明，miR-135a 可以下调 HIF-1α，并在 BM 来源的星形胶质细胞发育中发挥作用，为 BM 的治疗方法提供了新的理论视角。
