Differences in autophagy marker levels at birth in preterm vs. term infants

期刊论文
出版模式：

开放获取
发表日期：

2024年5月29日

查看全文

Noëmi Künstle,
Olga Gorlanova,
Andrea Marten,
Loretta Müller,
Pawan Sharma,
Martin Röösli,
Pablo Sinues,
Primo Schär,
David Schürmann,
Céline Rüttimann,
Carla Rebeca Da Silva Sena,
Uri Nahum,
Jakob Usemann,
Ruth Steinberg,
Sophie Yammine,
Sven Schulzke,
Philipp Latzin,
Urs Frey,
Fiona Beck,
Xenia Bovermann,
Carmen Casaulta,
Marion Curdy,
Carla Rebeca Da Silva Sena,
Kees de Hoogh,
Bettina Frauchiger,
Léa Kim-Mi Ho Dac,
Elisabeth Kieninger,
Insa Korten,
Marc-Alexander Oestreich,
Benjamin Stöcklin,
Carmen Streibel,
Florian Wyler

摘要

Background

Preterm infants are susceptible to oxidative stress and prone to respiratory diseases. Autophagy is an important defense mechanism against oxidative-stress-induced cell damage and involved in lung development and respiratory morbidity. We hypothesized that autophagy marker levels differ between preterm and term infants.

Methods

In the prospective Basel-Bern Infant Lung Development (BILD) birth cohort we compared cord blood levels of macroautophagy (Beclin-1, LC3B), selective autophagy (p62) and regulation of autophagy (SIRT1) in 64 preterm and 453 term infants.

Results

Beclin-1 and LC3B did not differ between preterm and term infants. However, p62 was higher (0.37, 95% confidence interval (CI) 0.05;0.69 in log2-transformed level, p = 0.025, p_adj = 0.050) and SIRT1 lower in preterm infants (−0.55, 95% CI −0.78;−0.31 in log2-transformed level, p_adj < 0.001). Furthermore, p62 decreased (p_adj-value for smoothing function was 0.018) and SIRT1 increased (0.10, 95% CI 0.07;0.13 in log2-transformed level, p_adj < 0.001) with increasing gestational age.

Conclusion

Our findings suggest differential levels of key autophagy markers between preterm and term infants. This adds to the knowledge of the sparsely studied field of autophagy mechanisms in preterm infants and might be linked to impaired oxidative stress response, preterm birth, impaired lung development and higher susceptibility to respiratory morbidity in preterm infants.

Impact

To the best of our knowledge, this is the first study to investigate autophagy marker levels between human preterm and term infants in a large population-based sample in cord blood plasma

This study demonstrates differential levels of key autophagy markers in preterm compared to term infants and an association with gestational age

This may be linked to impaired oxidative stress response or developmental aspects and provide bases for future studies investigating the association with respiratory morbidity