{
  "id": 4956989,
  "title": "Sphingolipid metabolism-related genes as key regulatory hubs in white smoke inhalation induced lung injury",
  "url": "https://urgent.news/2026/09/01/sphingolipid-metabolism-related-genes-as-key-regulatory-hubs-in-white",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-01T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.26.747407v1?rss=1"
  },
  "original_language": "en",
  "account": "White smoke inhalation injury (WSI) leads to significant lung damage, yet there are no targeted treatments available. Sphingolipid metabolism is thought to play a role in lung inflammation, but the specific transcriptional regulatory mechanisms in WSI have not been examined. This research aimed to identify key sphingolipid metabolism-related genes and explore their regulatory functions and potential therapeutic benefits in WSI.\n\nResearchers created a rat model of WSI and utilized multiple omics approaches, including bulk RNA sequencing, weighted gene coexpression network analysis, and single-cell RNA sequencing, to uncover differentially expressed sphingolipid metabolism-related genes (DESRGs). A protein-protein interaction network was employed to prioritize hub genes based on four centrality algorithms. Additionally, in silico gene knockout and molecular docking were performed to evaluate regulatory functions and identify potential drug candidates.\n\nFrom their data, the researchers identified 22 DESRGs that were mainly enriched in DNA replication and cell cycle pathways, rather than canonical sphingolipid metabolic processes. The protein-protein interaction network identified three key hub genes—Top2a, Ttk, and Ccna2—among which Top2a demonstrated the highest expression in epithelial cells and experienced the most substantial downregulation following smoke exposure. Single-cell RNA sequencing revealed infiltration of immune cells and distinct epithelial differentiation trajectories in WSI.\n\nVirtual gene knockout experiments indicated that Top2a depletion impacted the largest portion of the transcriptome (~0.4%) and was significantly enriched in processes such as lysosome biogenesis, innate immunity, phagocytosis, and lipid catabolism. Molecular docking studies revealed that thalidomide exhibited a high affinity for Top2a, with a Vina score of -8.5 kcal/mol, suggesting its potential as a therapeutic agent.\n\nIn conclusion, this multiomics integrative framework has identified Top2a as a central regulatory hub that links sphingolipid-associated inflammation to epithelial responses in WSI. The study also proposed thalidomide as a promising drug repurposing candidate for future translational investigation into treating WSI.",
  "summary": "Objective White smoke inhalation injury (WSI) causes severe acute lung damage with no specific therapy currently available. Sphingolipid metabolism is implicated in pulmonary inflammation, but its transcriptional regulatory landscape in WSI remains unexplored. This study aimed to identify key sphingolipid metabolism related genes and evaluate their regulatory roles and therapeutic potential in…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}