Foxo1-mediated inflammatory response after cerebral hemorrhage in rats.
The forkhead box O (Foxo) family of transcription factors plays a crucial role in cell apoptosis, immune regulation, and tissue development. Foxo1, as the foremost member of the Foxo family, regulates a wide range of molecular signals in many tissues, including tumor, liver, and brain. This study investigated Foxo1 expression at different time points and in different brain areas, and the role of Foxo1 in vivo in regulating inflammatory injury in a rat model of autologous blood-injected cerebral hemorrhage injury. We found that Foxo1 expression peaked at 12h post-intracerebral hemorrhage (ICH) and in the ipsilateral corpus striatum. Foxo1 knockdown by Foxo1 siRNA decreased ICH injury, improved neurological function, and decreased the expression of inflammatory factors downstream of the Foxo1 pathway, including TLR4, NF-κB, TNF-α, IL-1β, and IL-18. Foxo1 knockdown also decreased the expression and activity of myeloperoxidase, IL-1β, and IL-18. In conclusion, our findings demonstrate that Foxo1 is a key regulator of inflammatory injury in rats after ICH. By identifying the molecular mechanisms of Foxo1/TLR4/NF-κB signaling, we provide a novel rationale for therapeutic approaches to managing inflammatory injury after ICH.
Department of Pathophysiology, Chongqing Medical University, Chongqing, People's Republic of China.
Zhenyu
Z
Li
Department of Pathophysiology, Chongqing Medical University, Chongqing, People's Republic of China.
Qi
Q
He
Department of Neurosurgery, The Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Xuan
X
Zhai
Department of Pathophysiology, Chongqing Medical University, Chongqing, People's Republic of China.
Yan
Y
You
Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China.
Lingyu
L
Li
Department of Pathophysiology, Chongqing Medical University, Chongqing, People's Republic of China.
Yanghao
Y
Hou
Department of Emergency, The First Affiliated Hospital of Chongqing Medical University. Chongqing, People's Republic of China.
Faming
F
He
Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China.
Yong
Y
Zhao
Department of Pathophysiology, Chongqing Medical University, Chongqing, People's Republic of China. Electronic address: zjbingsheng@sina.com.
Jing
J
Zhao
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000150:complications / Q000378:metabolism*; D004660:Encephalitis / Q000150:complications / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071161:Forkhead Box Protein O1
D020382:Interleukin-18; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; D009195:Peroxidase; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1
Foxo1; Immunoregulation; Inflammatory injury; Intracerebral hemorrhage; MPO; TLR4