Autophagy-related genes expression in children with cystic fibrosis.

BACKGROUND: Autophagy is a self-degradative process that plays a role in removing misfolded or aggregated proteins located in the cytosol. Autophagy induction is initiated by the mammalian target of rapamycin (mTOR). Beclin-1, and microtubule-associated protein 1A/1B-light chain 3 (LC3) are proteins involved in the regulation of autophagy. Cystic fibrosis (CF) cells suffer from defective autophagy, related to altered proteostasis and chronic inflammation. The study aimed to assess the genetic expression of mTOR, Beclin-1, and LC3b in CF children and to correlate them with genotypes, phenotypes, and clinical severity of CF.

METHODS: A cross-sectional study included 31 CF patients and 31 healthy controls. Gene expression levels of Beclin-1, mTOR, and LC3b were quantified using quantitative PCR. Clinical severity was assessed through pulmonary function tests, Schwachman-Kulczycki score, and clinical and laboratory data.

RESULTS: Beclin-1 expression was significantly reduced in CF patients, while mTOR and LC3 were elevated. There were no statistically significant correlations between Beclin-1 levels and various demographic, clinical, or laboratory features in CF patients. There is a significant positive correlation between the mTOR gene and the Schwachman-Kulczycki score (r = 0.495, p = 0.005) and asthma-like symptoms (p = 0.026). The genetic expression of LC3b was markedly higher in patients with rectal prolapse, meconium ileus, and intestinal obstruction.

CONCLUSION: Beclin-1 expression was significantly reduced in CF patients compared to the control group. LC3b and mTOR expression levels were markedly elevated in CF patients indicating impairment of autophagy pathways in children with CF.