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NRF1 knockdown alleviates lipopolysaccharide-induced pulmonary inflammatory injury by upregulating DKK3 and inhibiting the GSK-3ß/ß-catenin pathway.
Kang, Le; Wang, Xinhua; Wang, Jianfang; Guo, Jing; Zhang, Wang; Lei, Ruirui.
Afiliación
  • Kang L; Department of Pediatrics, Neonatal Intensive Care Unit, Zhumadian Central Hospital, Zhumadian, Henan Province, China.
  • Wang X; Department of Pediatrics, Neonatal Intensive Care Unit, Zhumadian Central Hospital, Zhumadian, Henan Province, China.
  • Wang J; Department of Clinical Laboratory, Zhumadian Central Hospital, Zhumadian, Henan Province, China.
  • Guo J; Department of Pediatrics, Neonatal Intensive Care Unit, Henan Children's Hospital, Zhengzhou, Henan Province, China.
  • Zhang W; Department of Pediatrics, Neonatal Intensive Care Unit, Zhumadian Central Hospital, Zhumadian, Henan Province, China.
  • Lei R; Department of Neonatology, Zhumadian Central Hospital, Zhumadian, Henan Province, China.
Clin Exp Immunol ; 214(1): 120-129, 2023 12 11.
Article en En | MEDLINE | ID: mdl-37402316
ABSTRACT
Excessive inflammatory injury is the main cause of the incidence of severe neonatal pneumonia (NP) and associated deaths. Although dickkopf-3 (DKK3) exhibits anti-inflammatory activity in numerous pathological processes, its role in NP is still unknown. In this study, human embryonic lung WI-38 and MRC-5 cells were treated with lipopolysaccharide (LPS) to induce inflammatory injury of NP in vitro. The expression of DKK3 was downregulated in LPS-stimulated WI-38 and MRC-5 cells. DKK3 overexpression decreased LPS-induced inhibition of cell viability, and reduced LPS-induced apoptosis of WI-38 and MRC-5 cells. DKK3 overexpression also reduced LPS-induced production of pro-inflammatory factors such as ROS, IL-6, MCP-1, and TNF-α. Nuclear respiratory factors 1 (NRF1) knockdown was found to upregulate DKK3 and inactivate the GSK-3ß/ß-catenin pathway in LPS-injured WI-38 and MRC-5 cells. NRF1 knockdown also suppressed LPS-induced inhibition on cell viability, repressed LPS-induced apoptosis, and inhibited the accumulation of ROS, IL-6, MCP-1, and TNF-α in LPS-injured WI-38 and MRC-5 cells. DKK3 knockdown or re-activation of the GSK-3ß/ß-catenin pathway reversed the inhibitory effects of NRF1 knockdown on LPS-induced inflammatory injury. In conclusion, NRF1 knockdown can alleviate LPS-triggered inflammatory injury by regulating DKK3 and the GSK-3ß/ß-catenin pathway.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neumonía / Transducción de Señal Límite: Humans / Newborn Idioma: En Revista: Clin Exp Immunol Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neumonía / Transducción de Señal Límite: Humans / Newborn Idioma: En Revista: Clin Exp Immunol Año: 2023 Tipo del documento: Article País de afiliación: China