2. Academic Validation
  3. Ammonia-induced exosomal miRNA disrupts autophagy and promotes lung injury: Therapeutic potential of natural compounds

Ammonia-induced exosomal miRNA disrupts autophagy and promotes lung injury: Therapeutic potential of natural compounds

  • J Hazard Mater. 2026 Mar 15:506:141417. doi: 10.1016/j.jhazmat.2026.141417.
Yun Han 1,  Shiying Li 2,  Jian Yang 3,  Felix Kwame Amevor 4,  Md Ahsanul Kabir 5,  Xiaoling Zhao 6,  Yingjie Wang 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130. China; Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, College of Life Sciences, Sichuan University, Chengdu, Sichuan, China.
  • 2 State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China.
  • 3 Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, College of Life Sciences, Sichuan University, Chengdu, Sichuan, China.
  • 4 State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130. China.
  • 5 Biotechnology Division, Bangladesh Livestock Research Institute, Savar, Dhaka 1341, Bangladesh.
  • 6 State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China. Electronic address: [email protected].
  • 7 State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China. Electronic address: [email protected].
PMID: 41775203 DOI: 10.1016/j.jhazmat.2026.141417
Abstract

Ammonia (NH₃), a widespread agricultural emission, poses substantial risks to both humans and livestock through respiratory injury. However, the molecular mechanisms underlying ammonia-induced pulmonary damage remain poorly defined, and targeted interventions are unavailable. Using broiler chickens and primary alveolar type II (AT-II) cells, we investigated pathogenic pathways and potential protective agents. Exosomes derived from ammonia-exposed AT-II cells (NH₃-exo) were enriched in miR-20a-5p, which directly targeted PTEN, activated the Akt/mTOR pathway, and impaired autophagic flux, thereby intensifying inflammation and Apoptosis. Depletion of miR-20a-5p mitigated these effects in vitro and in vivo. Screening of six classes of natural compounds identified luteolin (flavonoid) and berberine (alkaloid) as the most effective protectants, restoring autophagic flux and reducing inflammatory and apoptotic responses, similar to rapamycin. This study identifies exosomal miR-20a-5p as a key mediator of ammonia toxicity and highlights Flavonoids and Alkaloids as promising natural candidates for mitigating ammonia-induced respiratory injury, with implications for agricultural and environmental health.

Keywords

Ammonia exposure; Autophagy dysregulation; Exosomal miRNA; PTEN; Pulmonary injury.

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