Bone morphogenetic protein 4 expression in the developing lumbosacral spinal cord of rat embryos with anorectal malformations. Issue 69 (October 2018)

• Record Type: Journal Article
• Authors: Yang, Zhonghua; Jia, Huimin; Bai, Yuzuo; Wang, Weilin
• Is Part Of: International journal of developmental neuroscience. Issue 69(2018:Oct.)
• Page Start: 32
• Page End: 38
• Publication Date: 2018-10
• Subjects: Lumbosacral spinal cord -- BMP4 -- Anorectal malformations; Developmental neurobiology -- Periodicals; Neurology -- Periodicals; Neurologie du développement -- Périodiques; Developmental neurobiology; Periodicals; 612.8
• DOI: 10.1016/j.ijdevneu.2018.06.006
• Languages: English
• ISSNs: 0736-5748

Abstract

Highlights: BMP4 plays an important role in the differentiation and proliferation of neural progenitor cells both in normal and anorectal malformation fetal rats. The decreased BMP4 expression found in the ARMs group was likely a factor involved in dysplasia of the lumbosacral spinal cord in these rats. That the phosphorylation of smad1/5 was not activated completely by declined BMP4 was possibly responsible for negative effect on transcriptional regulation in the nucleus and development of lumbosacral spinal cord in ARMs fetal rats. Abstract: Although there are improvements in treatment of anorectal malformations (ARMs), patients can still develop fecal incontinence, constipation, and soiling with loss in quality of life. Recent evidence suggests that malformations in the lumbosacral spinal cord are one of the factors that affect postoperative anorectal function. However, the underlying mechanism that produces these malformations has yet to be elucidated. The bone morphogenetic proteins (BMPs) comprise a large group of highly conserved molecules that are involved in multiple processes and play important roles in the formation, development, and differentiation of the spinal cord. This study was designed to investigate the levels of BMP4 expression in the lumbosacral spinal cord in ARMs rat embryos induced by ethylenethiourea (ETU). Specifically, we assessed the association of BMP4 levels with the maldevelopment of the lumbosacral spinal cord and whether BMP4 acted through the canonical intracellular pathway in embryonic rats with ARMs. BMP4 expression was confirmed with immunohistochemical staining, RT-qPCR and western blot analyses of embryonic day (E) 16, E17, E19 and E21 embryos, moreover Smad1/5 and pSmad1/5 expression were confirmed with western blot analyses at peak time point of BMP4 expression. Our results reveal that BMP4 expression in the lumbosacral spinal cord of ARMs rat embryos is decreased at both the mRNA and protein levels and could decrease the phosphorylation of smad1/5, when compared with their expression levels in normal tissue. These results also suggest that reductions in BMP4 expression were possibly responsible for dysfunction of the lumbosacral spinal cord during late developmental stages in ARMs fetal rats. Taken together, we conclude a role for BMP4 in the pathogenesis of lumbosacral spinal cord maldevelopment in developing ARMs rats.