Journal of pediatric surgery · 1999
Expression of RET proto-oncogene and GDNF deficit in Hirschsprung's disease.
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Zhan J, Xiu Y, Gu J, Fang Z, Hu X L
Аннотация
PURPOSE: The aim of this study was to investigate GDNF (glial cell line-derived neurotrophic factor) protein expression and RNA expression level of the RET proto-oncogene in human aganglionic (AG) bowel in Hirschsprung's disease (HD) and to further understand the pathophysiology of HD.
METHODS: To evaluate the possible implication of the RET gene and GDNF for the development of HD, mRNA expression level of the RETgene was examined by using the reverse transcription-polymerase chain reaction (RT-PCR) technique and protein expression level of the GDNF using an immunohistochemical technique in the bowel specimens of 15 HD patients.
RESULTS: A significantly less intense signal for RETmRNA was found in the AG bowel compared with the ganglionic bowel. In different age groups of patients, the intensities of RET level had similar results. In the same patients, there was strong GDNF immunoreactivity in the myenteric plexuse in ganglionic bowel. In the myenteron in AG bowel, the number of GDNF immunoreactive neuron cells was reduced significantly compared with normal ganglionic bowel.
CONCLUSIONS: From these preliminary data we conclude that the decreased RET expression in the AG bowel may suggest mal development of neural crest-derived cells in HD. The reduced level of GDNF in AG bowel may suggest a GDNF expression deficit interrupting the faithful signaling via RET, and both are implicated in the pathogenesis of HD.
METHODS: To evaluate the possible implication of the RET gene and GDNF for the development of HD, mRNA expression level of the RETgene was examined by using the reverse transcription-polymerase chain reaction (RT-PCR) technique and protein expression level of the GDNF using an immunohistochemical technique in the bowel specimens of 15 HD patients.
RESULTS: A significantly less intense signal for RETmRNA was found in the AG bowel compared with the ganglionic bowel. In different age groups of patients, the intensities of RET level had similar results. In the same patients, there was strong GDNF immunoreactivity in the myenteric plexuse in ganglionic bowel. In the myenteron in AG bowel, the number of GDNF immunoreactive neuron cells was reduced significantly compared with normal ganglionic bowel.
CONCLUSIONS: From these preliminary data we conclude that the decreased RET expression in the AG bowel may suggest mal development of neural crest-derived cells in HD. The reduced level of GDNF in AG bowel may suggest a GDNF expression deficit interrupting the faithful signaling via RET, and both are implicated in the pathogenesis of HD.
Предметные рубрики MeSH
Base SequenceChild, PreschoolCulture TechniquesDrosophila ProteinsFemaleGene ExpressionGlial Cell Line-Derived Neurotrophic FactorGlial Cell Line-Derived Neurotrophic Factor ReceptorsHirschsprung DiseaseHumansImmunohistochemistryInfantMaleMolecular Sequence DataNerve Growth FactorsNerve Tissue ProteinsProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins c-retRNA, MessengerReceptor Protein-Tyrosine KinasesReverse Transcriptase Polymerase Chain ReactionSensitivity and Specificity