Abstract
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.
Keywords
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Article info
Publication history
Published online: July 07, 2011
Accepted:
June 9,
2011
Received in revised form:
June 8,
2011
Received:
November 6,
2010
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
