Association of the TLR4-MyD88-JNK signaling pathway with inflammatory response in intracranial hemorrhage rats and its effect on neuronal apoptosis
Authors: Y-N Sun
D-J Huang
D Wan
Z-X Yang
Y Li
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Toll-like receptor 4; MyD88; JNK signaling pathway; inflammatory response; intracranial hemorrhage
Affiliations: Department of Neurosurgery and Neurointerventional, General Hospital of Ningxia Medical University, Yinchuan, China. .

Abstract:  Objective: To investigate the association of Toll-like receptor 4-myeloid differential protein-88- c-Jun N-terminal kinase (TLR4-MyD88-JNK) signaling pathway with inflammatory response in intracranial hemorrhage (ICH) rats and its effect on neuronal apoptosis. Patients and methods: The autologous blood was drawn and injected into the brain to establish the rat model of ICH (model group), and the control group was set up. The neurological behavior Longa score was given. The blood and brain tissues of rats were then collected to detect the serum indexes, including glucose (GLU), creatinine (CR), K+ and Na+, and the content of interleukin-6 (IL-6), IL-1Œ≤ and tumor necrosis factor-Œ± (TNF-Œ±) in each group. The neuronal apoptosis of brain tissues was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, the expressions of apoptosis- and TLR4-MyD88-JNK pathway-related genes and proteins were detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting. Finally, the association of TLR4-MyD88-JNK signaling pathway with the inflammatory response in ICH rats and its effect on neuronal apoptosis were completely observed. Results: MiR-23b was dramatically down-regulated in CC and the low miR-23b expressions were associated with the poor prognosis and worse OS of CC patients. Additionally, the functional assays demonstrated that miR-23b overexpression obviously repressed CC cell proliferation, invasion and migration abilities through the regulation of the AKT/mTOR pathway and the epithelial-to-mesenchymal transition (EMT) progress. Moreover, the luciferase reporter assay indicated that six1 was one functional target for miR-23b in CC cells, indicating that the inhibitory functions of miR-23b in CC cells were partially regulated by six1. Moreover, miR-23b restoration could prominently repress tumor growth in vivo. Conclusions: The TLR4-MyD88-JNK signaling pathway can facilitate the inflammatory response in ICH rats, thereby promoting the neuronal apoptosis. 

Retracted: No

PubPeer comments:
 Figure 2.  TUNEL staining. There are no significant positive cells in the control group, and the number of positive cells in the model group is markedly increased .  Despite different authorship, details of the Control panel seem to overlap with the Control and ATO panels of Fig 4 from [Zhu et al (2020) :  Apoptosis level of lung tissues in each group detected via TUNEL staining (magnification: 20u00d7). The number of TUNEL-positive cells in Model group is remarkably larger than that in Control group .  By extension those details also overlap with with Control and Model panels of Figure 3 from [Wang, Cheng Jiang] .  Apoptosis level of lung tissues in each group detected via TUNEL staining (magnification: 200u00d7). The number of TUNEL-positive cells in lung tissues in Ator group is remarkably larger than that of Model group .  ,