PURPOSE: CITED2 both modulates lung, heart and diaphragm development. The role of CITED2 in the pathogenesis of congenital diaphragmatic hernia (CDH) is unknown. We aimed to study CITED2 during abnormal lung development in the nitrofen model. METHODS: Timed-pregnant rats were given nitrofen on embryonic day (E) 9 to induce CDH. Fetal lungs were harvested on E15, 18 and 21. We performed RT-qPCR, RNAscope™ in situ hybridization and immunofluorescence staining for CITED2. RESULTS: We observed no difference in RT-qPCR (control: 1.09 ± 0.22 and nitrofen: 0.95 ± 0.18, p = 0.64) and in situ hybridization (1.03 ± 0.03; 1.04 ± 0.03, p = 0.97) for CITED2 expression in E15 nitrofen and control pups. At E18, CITED2 expression was reduced in in situ hybridization of nitrofen lungs (1.47 ± 0.05; 1.14 ± 0.07, p = 0.0006), but not altered in RT-qPCR (1.04 ± 0.16; 0.81 ± 0.13, p = 0.33). In E21 nitrofen lungs, CITED2 RNA expression was increased in RT-qPCR (1.04 ± 0.11; 1.52 ± 0.17, p = 0.03) and in situ hybridization (1.08 ± 0.07, 1.29 ± 0.04, p = 0.02). CITED2 protein abundance was higher in immunofluorescence staining of E21 nitrofen lungs (2.96 × 109 ± 0.13 × 109; 4.82 × 109 ± 0.25 × 109, p < 0.0001). CONCLUSION: Our data suggest that dysregulation of CITED2 contributes to abnormal lung development of CDH, as demonstrated by the distinct spatial-temporal distribution in nitrofen-induced lungs.
Hernias, Diaphragmatic, Congenital , Lung Diseases , Respiratory System Abnormalities , Animals , Female , Pregnancy , Rats , 2,4-Dinitrophenol , Disease Models, Animal , Gene Expression Regulation, Developmental , Hernias, Diaphragmatic, Congenital/chemically induced , Hernias, Diaphragmatic, Congenital/genetics , Hernias, Diaphragmatic, Congenital/metabolism , Lung/abnormalities , Lung Diseases/metabolism , Phenyl Ethers/toxicity , Rats, Sprague-Dawley
Years of extensive research have yielded much knowledge in many aspects of HIV-1 infection, treatments, and education. However, without a vaccine, the number of people infected worldwide continues to grow. The partial success of the Thai RV144 vaccine trial provides hope that a method of protection is indeed possible. Understanding the mechanism behind the protection is critical if we hope to achieve our goal of inhibiting new infections of HIV-1. We hypothesize that the Fc of IgG binding protein (Fcgbp) is associated with the protection observed in the RV144 vaccine trial. It has the ability to trap viral-antibody complexes in the mucosa by binding the Fc of IgG to Fcgbp. This property could be used in the form of a microbicide containing antibodies to a variety of HIV-1 epitopes to prevent sexual transmission of HIV-1. The aim of this paper is to stimulate further research into Fcgbp and its role in innate immunity.
