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KLF6 silencing attenuates MCAO-induced brain injury and cognitive dysfunction via targeting ferroptosis and
Hongyu Qian1, Sufang Zhou2, Rong Qian3
1Department of neurology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China. Hubei Sizhen Laboratory, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, China.
Introduction:
The incidence of cerebral ischemia-reperfusion injury (I/R) is complex which seriously threatens the life safety of patients. Neither its prevention nor its treatment has been successful so far. Proteins that bind to DNA and belong to the C2/H2 zinc finger family are known as Krüppel-like factors (KLFs). Among them, KLF6 plays a vital role in proliferation, metabolism, inflammation, and damage responses, although its function in I/R remains largely unexplored.
Methods:
In this study, we induced cerebral ischemia in rats using the middle cerebral artery occlusion (MCAO) model. Neural function, cerebral infarction volume, cognitive function, cortical pathological lesions, ferroptosis, and oxidative stress were measured.
Results:
Our findings indicated that the MCAO model exhibited signs of ferroptosis and a concurrent increase in KLF6 levels. Inhibition of KLF6 resulted in a significant decrease in the escape latency during swimming tests (p < .05), an increase in the frequency of platform crossings, and prolonged duration in the target quadrant compared to the control group. Additionally, silencing KLF6 mitigated MCAO-induced brain injury and reduced oxidative stress and ferroptosis, as evidenced by altered levels of Nrf2/HO-1 signaling proteins.
Discussion:
In conclusion, our results suggest that silencing KLF6 may protect against MCAO-induced pyroptosis, oxidative stress, and neurological dysfunction by inactivating the Nrf2/HO-1 signaling pathway. This study offers new perspectives on the molecular mechanisms related to MCAO and emphasizes the significance of targeting KLF6 for future therapeutic approaches.
Insights
Silencing Krüppel-like factor 6 (KLF6) protects against cerebral ischemia-reperfusion injury by reducing ferroptosis and oxidative stress. This finding highlights KLF6 as a potential therapeutic target for stroke treatment.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Cerebral ischemia-reperfusion injury (I/R) poses a significant threat to patient survival with limited therapeutic options.
- Krüppel-like factors (KLFs) are DNA-binding proteins involved in cellular processes, but KLF6's role in I/R injury is largely unknown.
Purpose of the Study:
- To investigate the role of Krüppel-like factor 6 (KLF6) in cerebral ischemia-reperfusion (I/R) injury.
- To explore the potential of targeting KLF6 for therapeutic interventions in I/R-induced brain damage.
Main Methods:
- Cerebral ischemia was induced in rats using the middle cerebral artery occlusion (MCAO) model.
- Evaluated neural function, infarct volume, cognitive deficits, pathological lesions, ferroptosis, and oxidative stress.
- Assessed the impact of KLF6 inhibition on MCAO-induced injury and Nrf2/HO-1 signaling.
Main Results:
- MCAO induced ferroptosis and increased KLF6 levels in the brain.
- Inhibiting KLF6 significantly improved cognitive function and reduced infarct size and brain injury.
- KLF6 silencing decreased oxidative stress and ferroptosis, modulating Nrf2/HO-1 signaling.
Conclusions:
- Silencing KLF6 demonstrates a protective effect against MCAO-induced brain injury, oxidative stress, and neurological deficits.
- KLF6 inactivation appears to mitigate injury by modulating the Nrf2/HO-1 signaling pathway.
- Targeting KLF6 presents a promising therapeutic strategy for managing cerebral I/R injury.
