ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Respiratory Pharmacology
Diacetyl-Induced Bronchiolitis Obliterans Involves Ubiquitin C Upregulation and Fibrosis-Related Gene Activation in Rats
Provisionally accepted
- 1Other
- 2Department of Central Laboratory, The Second Hospital of Shandong University, Jinan, China
- 3The Department of Paediatrics, The Second Hospital of Shandong University, Jinan, China
- 4Department of General Practice, The Second Hospital of Shandong University, Jinan, China
- 5Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
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Bronchiolitis obliterans (BO) is an irreversible, chronic obstructive pulmonary disease with inflammation and fibrosis causing bronchiolar narrowing. Inhaling diacetyl (DA) can result in BO in humans. In this study, we aimed to investigate the relationship between fibrosis-related gene expression and ubiquitin C (UbC) regulation in a rat model of BO following a single DA instillation, by examining lung histopathology, UbC protein levels, and transcriptomic changes. After DA exposure, rat bronchioles exhibited marked inflammation, increased collagen deposition, airway fibrosis, and obstruction. These changes were confirmed by histology and semi-quantitative image analysis. UbC protein levels were significantly elevated in a time-dependent manner. RNA sequencing revealed significant alterations in gene expression and enrichment of multiple molecular functions and biological processes in BO rats compared with controls, including pathways related to fibrosis formation and ubiquitin dysregulation. Quantitative PCR (qPCR) validation further confirmed the transcriptomic results, showing significant upregulation of Ube2t and Fap and downregulation of Cyp1a1, consistent with enhanced ubiquitin activity, fibroblast activation, and impaired oxidative stress regulation. These findings indicate that DA instillation induces early BO-like changes, disrupts ubiquitin regulation, and increases UbC expression, potentially through oxidative stress–related mechanisms. A better understanding of ubiquitin regulation (particularly UbC) may provide novel molecular targets for therapeutic intervention in BO.
Keywords: Bronchiolitis Obliterans, Diacetyl, Fibrosis, Ubiquitin C, Airway injury
Received: 23 Jul 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Wang, Jiang, Xiao, Geng, Ye and Ge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wei Ge, pediatr-gewei1982@outlook.com
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