Research Article| Volume 164, ISSUE 1-2, P51-61, October 28, 2011

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Neuronal loss and abnormal BMP/Smad signaling in the myenteric plexus of diabetic rats

  • Stella M. Honoré
    Dpto. Biología del Desarrollo, INSIBIO (Consejo Nacional de Investigaciones Científicas y Técnicas-Universidad Nacional de Tucumán (CONICET-UNT)), Chacabuco 461, T4000ILI San Miguel de Tucumán, Argentina
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  • Laura C. Zelarayan
    Max Delbruck Center for Molecular Medicine, Berlin, Germany
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  • Susana B. Genta
    Dpto. Biología del Desarrollo, INSIBIO (Consejo Nacional de Investigaciones Científicas y Técnicas-Universidad Nacional de Tucumán (CONICET-UNT)), Chacabuco 461, T4000ILI San Miguel de Tucumán, Argentina
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  • Sara S. Sánchez
    Corresponding author. Tel.: +49 54 381 4107214; fax: +49 54 381 4247752x7004.
    Dpto. Biología del Desarrollo, INSIBIO (Consejo Nacional de Investigaciones Científicas y Técnicas-Universidad Nacional de Tucumán (CONICET-UNT)), Chacabuco 461, T4000ILI San Miguel de Tucumán, Argentina
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      Bone morphogenetic proteins (BMPs) are critical molecules during gut morphogenesis. However, little is known about their participation in the homeostasis of adult gut and their possible role in diseases. Gastrointestinal complications occur during diabetes with loss of enteric neurons. In this study, we investigated the possible involvement of BMPs signaling pathway in diabetic enteric neuropathy in an experimental model of diabetes in rats. The expression of BMPs, BMPs receptors and intracellular Smad effectors were assessed in control and diabetic smooth muscle layer of jejunum by immunofluorescence, Western blot and RT-PCR methods. Myenteric neurons and glial cells were measured by immunofluorescence using specific markers. In addition, cell apoptosis was evaluated by means of direct and indirect techniques. We demonstrated that diabetic ganglia displayed a significant decrease in ganglion size due to enhanced apoptosis and loss of peripherin. A decrease in glial fibrillary acidic protein (GFAP protein) was also observed in enteric glial cells. BMP-2 was down-regulated in the myenteric plexus of diabetic rats at 3 and 9 weeks. A loss of enteric neurons by apoptosis was correlated with an ectopic BMP-4, increased BMPR-Ia and nuclear p-Smad1 expression in the myenteric plexus. Insulin-treatment prevented the intestinal alterations observed. These findings suggest that diabetes is associated with an abnormal BMP/Smad signaling expression in the myenteric ganglia that affects the homeostasis of the enteric plexus.


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