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Effect of insulin-like-growth factor and its receptors regarding lung development in fetal mice

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Abstract

In congenital diaphragmatic hernia (CDH), both mortality and morbidity are mainly caused by pulmonary hypoplasia and persistent pulmonary hypertension. Insulin-like growth factors (IGFs) are one of the growth factors that may play an important role in the fetal lung development. Elucidating the roles of these growth factors regarding fetal lung development would thus provide new insight regarding the optimal therapy for CDH patients. The aim of this study is to investigate the role of IGFs in the fetal lung development. The mRNA expression of IGFs and its receptors was analyzed by real-time RT-PCR from embryonic day (E) 11.5 to E18.5 mice. In addition, the lungs dissected from the E17.5 mice were divided into the following three groups; lungs cultured only in the serum-free medium (group I n = 5), lungs cultured in medium containing either IGF-I (group II n = 5), or IGF-II (group III n = 5). All cultures were investigated by immunohistochemistry, using the antibodies of thyroid transcription factor (TTF)-1, prosurfactant protein (proSp)-C, alpha smooth muscle actin (α-SMA), and anti-proliferating cell nuclear antigen (PCNA). The mRNA expression level of both IGF-I and IGF-II was higher during the earlier stage than that of later stage. In contrast, the mRNA expression of both IGF-I receptor (IGF-IR) and IGF-II receptor (IGF-IIR) was higher from the E17.5 to E18.5 than that at any other stage. The number of positive cells for TTF-1, proSp-C, α-SMA and PCNA increased more in both groups II and III than in group I. Based on our findings, IGFs are suggested to induce alveolar and vascular maturation in the late stages of fetal lung development. Therefore, the administration of IGFs to the fetal CDH lung may thus be able to effectively improve the symptoms of hypoplastic lung.

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Acknowledgments

The authors wish to thank Mr. Brian Quinn for reading the manuscript. This work was supported in part by Grant-in-Aid for Scientific Research from Japanese Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kouji Nagata, Kouji Masumoto, Toru Uesugi & Tomoaki Taguchi

  2. Faculty of Dental Science, Department of Pediatric Dentistry, Division of Oral Health, Growth and Development, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Shinya Yamamoto, Keigo Yoshizaki, Satoshi Fukumoto & Kazuaki Nonaka

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  1. Kouji Nagata
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  2. Kouji Masumoto
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  4. Shinya Yamamoto
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  8. Tomoaki Taguchi
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Correspondence to Kouji Masumoto.

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Nagata, K., Masumoto, K., Uesugi, T. et al. Effect of insulin-like-growth factor and its receptors regarding lung development in fetal mice. Pediatr Surg Int 23, 953–959 (2007). https://doi.org/10.1007/s00383-007-1977-8

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  • DOI: https://doi.org/10.1007/s00383-007-1977-8

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