PT  - JOURNAL ARTICLE
AU  - Stefan Dehmel
AU  - Agnieszka Pastula
AU  - Rabea Imker
AU  - Nikola Schulz
AU  - Oliver Eickelberg
AU  - Adalbert Roscher
AU  - Susanne Krauss-Etschmann
TI  - Late-breaking abstract: Maternal genetic asthma predisposition affects pulmonary microRNA profiles in neonatal offspring
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p1128
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p1128.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p1128.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Introduction: Exposure-induced deregulation of microRNAs (miRs) during early critical developmental periods has been proposed to contribute to the propagation of asthma risk in later life.Aim: We asked if maternal genetic asthma predisposition is sufficient to affect pulmonary miR profiles in offspring that do not bear the genetic asthma risk. To address this question, we used female mice with a heterozygous deficiency for Tbx21 as they develop spontaneous airway remodeling and airway hyperreactivity (Finotto et al., Science, 2002; 295:336).Methods: Female C57BL/6J Tbx21+/- mice were mated with WT males. Neonatal lungs from male WT offspring of dams with (Tbx21+/-, n=5) and without genetic asthma predisposition (WT, n=3) were removed within 24h after birth and total mRNA including small RNAs was extracted. Duplicate pools of RNAs were subjected to miR expression profiling (ABI, TaqMan® Array microRNA cards). In silico target prediction was performed for miRs with a >1.5x change followed by pathway analysis (DIANA-mirpath, TargetScan).Results: Male WT offspring of Tbx21+/- dams showed an up-regulation of 14 of 750 miRs (1.5-2.1x), while 17 miRs were down-regulated (1.5-4.7x) compared to male WT offspring of dams without genetic asthma predisposition. Pathway analysis showed a significant enrichment of target genes within the WNT pathway (49 of 154 genes). MiRs 27a* and 124 were found to target multiple genes (≥15) in the WNT pathway suggesting a key regulatory function for these miRs in WNT signaling.Conclusion: These data show that maternal genetic asthma predisposition affects pulmonary miR profiles during an early developmental stage and might therefore influence lung development.