Knockdown of KLK13 has a protective effect against ovalbumin-induced asthma in mice.

Abstract

BACKGROUND: Asthma remains a critical global health concern impacting diverse age groups, with incidence rates rising continuously. Recent studies have identified elevated levels of kallikrein-related peptidase 13 (KLK13) in nasal lavage specimens of asthma patients; however, its functional mechanisms remain explored. METHODS: An experimental asthma model was established in mice through ovalbumin (OVA) sensitization with an Al(OH)adjuvant. The role of KLK13 was evaluated using immunohistochemistry, hematoxylin-eosin, and Masson trichrome staining, pulmonary function testing, enzyme-linked immunosorbent serological assay (ELISA), biochemical measurements, and immunoblotting. RESULTS: OVA-challenged mice exhibited marked upregulation of KLK13 expression. Genetic silencing of KLK13 reduced airway hyperresponsiveness in the asthma model. Histological analysis showed that OVA exposure caused extensive peribronchial inflammatory cell infiltration, bronchial wall thickening with luminal narrowing, and pulmonary collagen accumulation, all of which were significantly improved by KLK13 knockdown. OVA administration also induced substantial increases in interleukin (IL)-4, IL-5, IL-13, and immunoglobulin E, while KLK13 silencing significantly attenuated these elevations. Biochemical assays revealed increased malonaldehyde content and reactive oxygen species generation, alongside decreased superoxide dismutase activity and glutathione peroxidase levels in OVA-exposed mice; these changes were effectively normalized by KLK13 knockdown. At the molecular level, KLK13 inhibition reduced phosphorylation of inhibitor of nuclear factor-κB (NF-κB) alpha and p65 subunits, thereby suppressing activation of NF-κB pathway in OVA-induced asthma. CONCLUSION: KLK13 depletion ameliorates asthmatic pathology by reducing airway inflammation, preventing structural remodeling, and restoring redox balance, primarily through NF-κB signaling modulation.