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Kif7 expression is decreased in the diaphragmatic and pulmonary mesenchyme of nitrofen-induced congenital diaphragmatic hernia.

Authors: Takahashi, T  Friedmacher, F  Takahashi, H  Hofmann, AD  Puri, P 
Citation: Takahashi T, etal., J Pediatr Surg. 2015 Jun;50(6):904-7. doi: 10.1016/j.jpedsurg.2015.03.058. Epub 2015 Apr 11.
Pubmed: (View Article at PubMed) PMID:25921351
DOI: Full-text: DOI:10.1016/j.jpedsurg.2015.03.058

PURPOSE: Developmental mutations that inhibit diaphragmatic and pulmonary mesenchyme formation have been shown to cause congenital diaphragmatic hernia (CDH) and pulmonary hypoplasia (PH). Kinesin family member 7 (Kif7) plays a crucial role in diaphragmatic and pulmonary morphogenesis by controlling proliferation of mesenchymal cells. Loss of Kif7 has been reported to result in diaphragmatic defects and PH. We hypothesized that diaphragmatic and pulmonary Kif7 expression is decreased in the nitrofen-induced CDH model. METHODS: Timed-pregnant rats were exposed to either nitrofen or vehicle on gestational day 9 (D9). Fetal diaphragms and lungs were microdissected on D13, D15, and D18, and divided into control and nitrofen-exposed specimens. Gene expression levels of Kif7 were analyzed by qPCR. Immunohistochemical staining was performed to evaluate Kif7 protein expression. RESULTS: Relative mRNA expression of Kif7 was significantly reduced in pleuroperitoneal folds (D13), developing diaphragms and lungs (D15), and fully muscularized diaphragms and differentiated lungs (D18) of nitrofen-exposed fetuses compared to controls. Immunoreactivity/immunofluorescence of Kif7 was markedly decreased in diaphragmatic and pulmonary mesenchyme of nitrofen-exposed fetuses on D13, D15, and D18 compared to controls. CONCLUSION: Decreased Kif7 expression during diaphragmatic development may interfere with mesenchymal cell proliferation, leading to defective pleuroperitoneal folds, and resulting in diaphragmatic defects and associated PH in the nitrofen-induced CDH model.

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CRRD Object Information
CRRD ID: 11553839
Created: 2016-10-14
Species: All species
Last Modified: 2016-10-14
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.