Downregulation of miR-26b attenuates early brain injury induced by subarachnoid hemorrhage via mediating the KLF4/STAT3/HMGB1 axis

Huang, Zewei1; Liu, Jialin2; Xu, Jiongfu3; Dai, Limeng3,5; Wang, Hao3,4,5

2023

10.1016/j.expneurol.2022.114270

EXPERIMENTAL NEUROLOGY   Impact Factor & Quartile

0014-4886

1090-2430

Background: Early brain injury (EBI) refers to early-onset secondary complications that occur after subarachnoid hemorrhage (SAH), and associated with high rate of disability and mortality. Recent investigations have indi-cated microRNA-26b (miR-26b) as a biomarker in the progression of SAH. Accordingly, the present study was designed to elucidate the role of miR-26b in influencing EBI following SAH and the downstream mechanisms.Methods: Firstly, SAH rat models and neuron injury models were developed to assess the effect of miR-26b on EBI-like symptoms and subsequent inflammation. Dual-luciferase reporter gene assay was further implemented to evaluate the binding of miR-26b to its putative target gene STAT3. Loss-of-function and rescue experiments were performed to assess the functionality of miR-26b-mediated STAT3 in both models.Results: miR-26b was found to target KLF4 and negative-modulate its expression, whereby aggravating EBI and inflammatory response in SAH rat models and stimulating hemoglobin-induced apoptosis in astrocytes. On the other hand, silencing of miR-26b reversed these changes in SAH rat models and hemoglobin (Hb)-induced as-trocytes. miR-26b could further activate STAT3 via down-regulation of KLF4. Furthermore, KLF4 knockdown up -regulated HMGB1 to aggravate EBI following SAH.Conclusions: Collectively, our findings highlighted the ameliorative effect of miR-26b inhibition on EBI in SAH and the possible mechanism associated with the KLF4/STAT3/HMGB1 axis.

microRNA-26b Subarachnoid hemorrhage Early brain injury Kr?ppel-like Factor-4 Signal transducer and activator of transcription 3 High mobility group box chromosomal protein 1

SCI

English

First ; Corresponding

[ZDSYS20200811142804014] ; [SZXK045] ; [JCYJ20210324114008023]

Neurosciences & Neurology

Neurosciences

WOS:000890330600003

ACADEMIC PRESS INC ELSEVIER SCIENCE

NEUROSCIENCE & BEHAVIOR

Web of Science

1.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Dept Crit Care Med,Clin Med Coll 2,Affiliated Hosp, Shenzhen 518020, Peoples R China
2.Shijiazhuang Huayao Hosp North China Med & Hlth Gr, Dept Neurol, Shijiazhuang 050000, Peoples R China
3.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Peoples Hosp, Dept Neurosurg,Clin Med Coll 2,Jinan Univ, Shenzhen 518020, Peoples R China
4.Guangdong Engn Technol Res Ctr Nervous Anat & Rela, Shenzhen 518020, Peoples R China
5.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Dept Neurosurg, Clin Med Coll 2,Jinan Univ,Affiliated Hosp 1, 1017 Dongmen North Rd, Shenzhen 518020, Guangdong, Peoples R China

Huang, Zewei,Liu, Jialin,Xu, Jiongfu,et al. Downregulation of miR-26b attenuates early brain injury induced by subarachnoid hemorrhage via mediating the KLF4/STAT3/HMGB1 axis[J]. EXPERIMENTAL NEUROLOGY,2023,359.

Huang, Zewei,Liu, Jialin,Xu, Jiongfu,Dai, Limeng,&Wang, Hao.(2023).Downregulation of miR-26b attenuates early brain injury induced by subarachnoid hemorrhage via mediating the KLF4/STAT3/HMGB1 axis.EXPERIMENTAL NEUROLOGY,359.

Huang, Zewei,et al."Downregulation of miR-26b attenuates early brain injury induced by subarachnoid hemorrhage via mediating the KLF4/STAT3/HMGB1 axis".EXPERIMENTAL NEUROLOGY 359(2023).