Scholarlink

Background <p>Pediatric sepsis, a major cause of acute lung injury (ALI), involves a dysregulated host response. Cuproptosis is a novel copper-dependent cell death process regulated by Ferredoxin 1 (FDX1). However, its role in pediatric sepsis-associated ALI is unknown. This study investigated the upstream regulation mechanism of FDX1, and its role in pediatric sepsis-related ALI.</p> Methods <p>Peripheral blood mononuclear cells (PBMCs) were collected from septic children and healthy controls. All enrolled pediatric subjects were divided into three groups: healthy control group (<i>N</i> = 40), sepsis without ALI group (<i>N</i> = 30), and sepsis with ALI group (<i>N</i> = 30). The clinical significance of FDX1, steroidogenic factor 1 (SF1), and Jun proto-oncogene (cJUN) was assessed by qRT-PCR. A septic ALI cell model was established using LPS-treated BEAS-2B cells. Functional assays (CCK-8, TUNEL, ELISA) assessed viability, apoptosis, and inflammation. An in vivo cecal ligation and puncture (CLP) model was employed to confirm the role of FDX1. Molecular mechanisms (transcriptional regulation, protein interaction) were examined via ChIP, dual-luciferase, and Co-IP.</p> Results <p>FDX1, SF1, and cJUN levels were significantly elevated in pediatric sepsis patients, especially in those complicated with ALI, and the three genes were positively correlated with each other. In vitro, LPS induced BEAS-2B cell injury, inflammation, and cuproptosis. FDX1 overexpression exacerbated these effects, while its knockdown exerted protective effects. Mechanistically, SF1 directly bound to the FDX1 promoter to activate its transcription. SF1 physically interacted with cJUN, and they synergistically enhanced FDX1 transcription. Knockdown of cJUN abolished SF1-mediated FDX1 upregulation and its pro-cuproptotic effects. In vivo experiments demonstrated that FDX1 knockdown attenuated CLP-induced lung injury, inflammation, and cuproptosis.</p> Conclusions <p>SF1, cJUN, and FDX1 may be closely involved in pediatric sepsis-related ALI. The physical interaction between SF1 and cJUN potentially modulates FDX1 transcription, which may contribute to cuproptosis and pediatric sepsis-related ALI progression.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

SF1 regulates the transcription of FDX1 to promote cuproptosis in pediatric sepsis-related acute lung injury by interacting with cJUN

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月30日

查看全文
  • Yanrong Wang,
  • Junhua Sun,
  • Lifen Zhang,
  • Shenghu Zhou,
  • Fang Zhao

摘要

Background

Pediatric sepsis, a major cause of acute lung injury (ALI), involves a dysregulated host response. Cuproptosis is a novel copper-dependent cell death process regulated by Ferredoxin 1 (FDX1). However, its role in pediatric sepsis-associated ALI is unknown. This study investigated the upstream regulation mechanism of FDX1, and its role in pediatric sepsis-related ALI.

Methods

Peripheral blood mononuclear cells (PBMCs) were collected from septic children and healthy controls. All enrolled pediatric subjects were divided into three groups: healthy control group (N = 40), sepsis without ALI group (N = 30), and sepsis with ALI group (N = 30). The clinical significance of FDX1, steroidogenic factor 1 (SF1), and Jun proto-oncogene (cJUN) was assessed by qRT-PCR. A septic ALI cell model was established using LPS-treated BEAS-2B cells. Functional assays (CCK-8, TUNEL, ELISA) assessed viability, apoptosis, and inflammation. An in vivo cecal ligation and puncture (CLP) model was employed to confirm the role of FDX1. Molecular mechanisms (transcriptional regulation, protein interaction) were examined via ChIP, dual-luciferase, and Co-IP.

Results

FDX1, SF1, and cJUN levels were significantly elevated in pediatric sepsis patients, especially in those complicated with ALI, and the three genes were positively correlated with each other. In vitro, LPS induced BEAS-2B cell injury, inflammation, and cuproptosis. FDX1 overexpression exacerbated these effects, while its knockdown exerted protective effects. Mechanistically, SF1 directly bound to the FDX1 promoter to activate its transcription. SF1 physically interacted with cJUN, and they synergistically enhanced FDX1 transcription. Knockdown of cJUN abolished SF1-mediated FDX1 upregulation and its pro-cuproptotic effects. In vivo experiments demonstrated that FDX1 knockdown attenuated CLP-induced lung injury, inflammation, and cuproptosis.

Conclusions

SF1, cJUN, and FDX1 may be closely involved in pediatric sepsis-related ALI. The physical interaction between SF1 and cJUN potentially modulates FDX1 transcription, which may contribute to cuproptosis and pediatric sepsis-related ALI progression.