Congenital diaphragmatic hernia (CDH) is a common life-threatening congenital anomaly resulting in high rates of perinatal death and neonatal respiratory distress. Some of the nonisolated forms are related to single-gene mutations or genomic rearrangements, but the genetics of the isolated forms (60% of cases) still remains a challenging issue. Retinoid signaling (RA) is critical for both diaphragm and lung development, and it has been hypothesized that subtle disruptions of this pathway could contribute to isolated CDH etiology. Here we used time series of normal and CDH lungs in humans, in nitrofen-exposed rats, and in surgically induced hernia in rabbits to perform a systematic transcriptional analysis of the RA pathway key components. The results point to CRPBP2, CY26B1, and ALDH1A2 as deregulated RA signaling genes in human CDH. Furthermore, the expression profile comparisons suggest that ALDH1A2 overexpression is not a primary event, but rather a consequence of the CDH-induced lung injury. Taken together, these data show that RA signaling disruption is part of CDH pathogenesis, and also that dysregulation of this pathway should be considered organ specifically.

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American Journal of Physiology: Lung Cellular and Molecular Physiology
Department of Pediatric Surgery

Coste, K, Beurkens, L.W.J.E, Blanc, P, Gallot, D, Delabaere, A, Blanchon, L, … Sapin, V. (2015). Metabolic disturbances of the vitamin A pathway in human diaphragmatic hernia. American Journal of Physiology: Lung Cellular and Molecular Physiology, 308(2), L147–L157. doi:10.1152/ajplung.00108.2014