Decreased ubiquitin modifying enzyme A20 associated with hyper-responsiveness to ovalbumin challenge following intrauterine growth restriction

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BACKGROUND: Intrauterine growth restriction (IUGR) is strongly correlated with an increased risk of asthma later in life. Farm dust protects mice from developing house dust mite-induced asthma, and loss of ubiquitin modifying enzyme A20 in lung epithelium would abolish this protective effect. However, the mechanisms of A20 in the development of asthma following IUGR remains unknown. METHODS: An IUGR rat model induced by maternal nutrient restriction was used for investigating the role of A20 in the response characteristics of IUGR rats to ovalbumin (OVA) challenge. The ubiquitination of proteins and N6-methyladenosine (m6A) modifications were used to further assess the potential mechanism of A20. RESULTS: IUGR can reduce the expression of A20 protein in lung tissue of newborn rats and continue until 10 weeks after birth. OVA challenging can increase the expression of A20 protein in lung tissue of IUGR rats, but its level was still significantly lower than the control OVA group. The differentially ubiquitinated proteins in lung tissues were also observed in IUGR and normal newborn rats. Furthermore, this ubiquitination phenomenon continued from the newborn to adulthood. In the detected RNA methylations, m6A abundance of the motif GGACA was the highest. The higher abundances of m6A modification of A20 mRNA from IUGR were negatively correlated with the trend of A20 protein levels. CONCLUSION: These findings indicate A20 as a key regulator during the development of asthma following IUGR, providing further insight into the prevention of asthma induced by environmental factors.

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