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MicroRNA-135a participates in the development of astrocytes derived from bacterial meningitis by downregulating HIF-1 alpha

Artikel i vetenskaplig tidskrift
Författare Y. Dung
J. Wang
K. X. Du
T. M. Jia
Changlian Zhu
Y. Zhang
F. L. Xu
Publicerad i American Journal of Physiology-Cell Physiology
Volym 316
Nummer/häfte 5
Sidor C711-C721
ISSN 0363-6143
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi
Sidor C711-C721
Språk en
Länkar dx.doi.org/10.1152/ajpcell.00440.20...
Ämnesord astrocyte, bacterial meningitis, HIF-1 alpha, microRNA-135a, cell-proliferation, expression, activation, infection, apoptosis, protein, cloning, injury, axis
Ämneskategorier Neurovetenskaper

Sammanfattning

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 Streptococcus pneumoniae to establish the BM model. The expression of miR-135a and hypoxia-inducible factor 1 alpha (HIF-1 alpha) 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-1 alpha was also determined along with the overexpression or knockdown of HIF-1 alpha. The results obtained indicated that miR-135a was poorly expressed, whereas HIF-1 alpha 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-1 alpha expression was determined to be diminished by miR-135a. The upregulation of HIF-1 alpha 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-1 alpha and play a contributory role in the development of astrocytes derived from BM. providing a novel theoretical perspective for BM treatment approaches.

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