1. Academic Validation
  2. Bacterial cellulose repairs asthmatic epithelial injury by reprogramming CDS1-mediated phosphatidylinositol metabolism to inhibit PI3K/AKT signaling

Bacterial cellulose repairs asthmatic epithelial injury by reprogramming CDS1-mediated phosphatidylinositol metabolism to inhibit PI3K/AKT signaling

  • Int J Biol Macromol. 2025 Dec 16;338(Pt 2):149695. doi: 10.1016/j.ijbiomac.2025.149695.
Qi Yu 1 Liping Huang 2 Zhuman Wu 1 Jinzhong Zhuo 1 Haohua Huang 1 Yixin Cheng 1 Mingxuan Hu 1 Qiong Wang 3 Dongyu Liu 1 Xiaoxiao Jiang 1 Jinming Zhang 4 Shaoxi Cai 5 Hangming Dong 6
Affiliations

Affiliations

  • 1 Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China, 510515.
  • 2 Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China, 510515; Department of Respiratory and Critical Care Medicine, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, China.
  • 3 YI CHANG Nano New Materials Technology(Guangdong) Co., LTD, 510000, Guangzhou, China.
  • 4 Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China, 510515. Electronic address: [email protected].
  • 5 Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China, 510515. Electronic address: [email protected].
  • 6 Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China, 510515. Electronic address: [email protected].
Abstract

Asthma is a common respiratory disease characterized by chronic inflammation and airway obstruction, with airway epithelial damage playing a pivotal role in pathogenesis. Existing treatments regulate inflammation without addressing epithelial barrier repair, indicating the need for therapeutic agents that target damaged epithelial cells. This study evaluates the effects of Bacterial cellulose (BC), a biocompatible polymer with anti-inflammatory and pro-regenerative properties, as a promising therapeutic candidate for asthma. In a mouse model of house dust Mite (HDM)-induced allergic asthma, intranasal BC administration markedly reduces both airway inflammation and mucus hypersecretion while also improving epithelial barrier integrity. Bronchoalveolar lavage fluid (BALF) metabolomics and single-cell RNA Sequencing of human asthmatic epithelium samples reveal that BC downregulates epithelial CDP-diacyl glycerol synthase 1 (CDS1), resulting in decreased synthesis of phosphatidylinositol (PI) and PI 4,5- bisphosphate (PI(4,5)P₂) and suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling. CDS1 overexpression reverses the effect of BC on asthma in vivo, confirming that CDS1 is a key target. BC administration alleviates asthma by repairing the epithelial barrier and inhibiting PI3K/Akt signaling via CDS1-dependent PI reprogramming. Thus, treatment with BC represents a promising therapeutic strategy for asthma, with dual actions in repairing epithelial barrier dysfunction and mitigating inflammation.

Keywords

Airway epithelium; Asthma; Bacterial cellulose; CDP-diacyl glycerol synthase 1; Metabolic reprogramming; PI3K/AKT pathway.

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