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Micro RNA ‐211 causes ganglion cell dysplasia in congenital intestinal atresia via down‐regulation of glial‐derived neurotrophic factor
Author(s) -
Xia Z.q.,
Ding D.k.,
Zhang N.,
Wang J.x.,
Yang H.y.,
Zhang D.
Publication year - 2016
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12705
Subject(s) - glial cell line derived neurotrophic factor , neurotrophic factors , ganglion , microbiology and biotechnology , neurotrophin , brain derived neurotrophic factor , biology , neuroscience , medicine , receptor
Background Micro RNA s (mi RNA s) are known to be involved in normal brain functions and nervous system diseases. Some evidence have pointed to the dysregulation of mi RNA s in congenital intestinal atresia. In this study, we investigated the differential expression of mi RNA s and the posttranscriptional regulation of glial‐derived neurotrophic factor ( GDNF ) by endogenous mi RNA in congenital intestinal atresia. Methods Quantitative real‐time PCR and a Western blot were performed to determine the regulation of mi RNA and GDNF in patients with congenital intestinal atresia. The results were verified in rat model of intestinal atresia and bone marrow derived stem cell BMSC s‐derived into intestinal ganglion cells. The effects of mi RNA and GDNF on the cell proliferation and apoptosis of isolated intestinal ganglion cells were detected with an 3‐(4,5‐dimethylthiazol)‐2,5‐diphenyl tetrazolium ( MTT ) assay and a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. Key Results Only miR‐211 was greatly up‐regulated in the patients with congenital intestinal atresia. The other mi RNA s examined showed no change. Overexpression of miR‐211 suppressed the differentiation of BMSC s into intestinal ganglion cells. In retinal ganglion cells ( RGC ‐5 cells), miR‐211 regulated the expression of GDNF . The MTT and TUNEL assays revealed that miR‐211 overexpression suppressed the cell proliferation of isolated intestinal ganglion cells and that GDNF overexpression reversed the effect of pre‐miR‐211 on cell proliferation and apoptosis. Conclusions & Inferences Our results indicate that overexpression of miR‐211 suppresses the differentiation of BMSC s into intestinal ganglion cells by directly down‐regulating the expression of GDNF . The findings elucidate the role of mi RNA in congenital intestinal atresia.