1. Academic Validation
  2. Branched-chain amino acid transaminase 1 inhibition attenuates childhood asthma in mice by effecting airway remodeling and autophagy

Branched-chain amino acid transaminase 1 inhibition attenuates childhood asthma in mice by effecting airway remodeling and autophagy

  • Respir Physiol Neurobiol. 2022 Dec;306:103961. doi: 10.1016/j.resp.2022.103961.
Jing Li 1 Meixue Chen 2 Lingling Lu 2 Jinfeng Wang 2 Liling Tan 2
Affiliations

Affiliations

  • 1 Department of Pediatrics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China. Electronic address: Li0829manman@126.com.
  • 2 Department of Pediatrics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.
Abstract

Childhood asthma is a common chronic childhood disease. Branched-chain amino acid transaminase 1 (BCAT1) was reported to be upregulated in chronic airway diseases, while its role in childhood asthma is unclear. Asthma mouse models were established in neonatal mice by 10 µg ovalbumin (OVA) intraperitoneal injection and 3% OVA inhalational challenge. In OVA-challenged mice, BCAT1 levels were upregulated. BCAT1 inhibitor alleviated airway structure and inflammation by suppressing IgE, OVA-specific IgE and inflammatory cytokine release and inflammatory cell infiltration. BCAT1 inhibitor alleviated airway remodeling by inhibiting goblet cell hyperplasia, mucus secretion and the expression of α-SMA and collagen I/III. The BCAT1 inhibitor prevented OVA-enhanced Autophagy by decreasing Beclin-1, Atg5 and LC3I/II and increasing p65 levels. In IL-13-stimulated BEAS-2B cells, rapamycin promoted inflammatory cytokine release and Autophagy after BCAT1 inhibitor administration. Our research revealed that BCAT1 was upregulated in neonatal asthmatic mice and that a BCAT1 inhibitor might restrain airway inflammation and remodeling by decreasing Autophagy, which offered a novel mechanistic understanding of childhood asthma.

Keywords

Airway remodeling; Autophagy; BCAT1; Child, asthma; Inflammation.

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