Gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia

Idiopathic achalasia is characterized by the absence of peristalsis secondary to loss of neurons in the myenteric plexus that hampers proper relaxation of the lower esophageal sphincter. Achalasia can be considered a multifactorial disorder as it occurs in related individuals and is associated with...

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Main Authors:	Palmieri, Orazio, Mazza, Tommaso, Merla, Antonio, Fusilli, Caterina, Cuttitta, Antonello, Martino, Giuseppina, Latiano, Tiziana, Corritore, Giuseppe, Bossa, Fabrizio, Palumbo, Orazio, Muscarella, Lucia Anna, Carella, Massimo, Graziano, Paolo, Andriulli, Angelo, Latiano, Anna
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980661/

id	pubmed-4980661
recordtype	oai_dc
spelling	pubmed-49806612016-08-19 Gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia Palmieri, Orazio Mazza, Tommaso Merla, Antonio Fusilli, Caterina Cuttitta, Antonello Martino, Giuseppina Latiano, Tiziana Corritore, Giuseppe Bossa, Fabrizio Palumbo, Orazio Muscarella, Lucia Anna Carella, Massimo Graziano, Paolo Andriulli, Angelo Latiano, Anna Article Idiopathic achalasia is characterized by the absence of peristalsis secondary to loss of neurons in the myenteric plexus that hampers proper relaxation of the lower esophageal sphincter. Achalasia can be considered a multifactorial disorder as it occurs in related individuals and is associated with HLA class II genes, thereby suggesting genetic influence. We used microarray technology and advanced in-silico functional analyses to perform the first genome-wide expression profiling of mRNA in tissue samples from 12 achalasia and 5 control patients. It revealed 1,728 differentially expressed genes, of these, 837 (48.4%) were up-regulated in cases. In particular, genes participating to the smooth muscle contraction biological function were mostly up-regulated. Functional analysis revealed a significant enrichment of neuronal/muscular and neuronal/immunity processes. Upstream regulatory analysis of 180 genes involved in these processes suggested TLR4 and IL18 as critical key-players. Two functional gene networks were significantly over-represented: one involved in organ morphology, skeletal muscle system development and function, and neurological diseases, and the other participating in cell morphology, humoral immune response and cellular movement. These results highlight on pivotal genes that may play critical roles in neuronal/muscular and neuronal/immunity processes, and that may contribute to the onset and development of achalasia. Nature Publishing Group 2016-08-11 /pmc/articles/PMC4980661/ /pubmed/27511445 http://dx.doi.org/10.1038/srep31549 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Palmieri, Orazio Mazza, Tommaso Merla, Antonio Fusilli, Caterina Cuttitta, Antonello Martino, Giuseppina Latiano, Tiziana Corritore, Giuseppe Bossa, Fabrizio Palumbo, Orazio Muscarella, Lucia Anna Carella, Massimo Graziano, Paolo Andriulli, Angelo Latiano, Anna
spellingShingle	Palmieri, Orazio Mazza, Tommaso Merla, Antonio Fusilli, Caterina Cuttitta, Antonello Martino, Giuseppina Latiano, Tiziana Corritore, Giuseppe Bossa, Fabrizio Palumbo, Orazio Muscarella, Lucia Anna Carella, Massimo Graziano, Paolo Andriulli, Angelo Latiano, Anna Gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia
author_facet	Palmieri, Orazio Mazza, Tommaso Merla, Antonio Fusilli, Caterina Cuttitta, Antonello Martino, Giuseppina Latiano, Tiziana Corritore, Giuseppe Bossa, Fabrizio Palumbo, Orazio Muscarella, Lucia Anna Carella, Massimo Graziano, Paolo Andriulli, Angelo Latiano, Anna
author_sort	Palmieri, Orazio
title	Gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia
title_short	Gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia
title_full	Gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia
title_fullStr	Gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia
title_full_unstemmed	Gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia
title_sort	gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia
description	Idiopathic achalasia is characterized by the absence of peristalsis secondary to loss of neurons in the myenteric plexus that hampers proper relaxation of the lower esophageal sphincter. Achalasia can be considered a multifactorial disorder as it occurs in related individuals and is associated with HLA class II genes, thereby suggesting genetic influence. We used microarray technology and advanced in-silico functional analyses to perform the first genome-wide expression profiling of mRNA in tissue samples from 12 achalasia and 5 control patients. It revealed 1,728 differentially expressed genes, of these, 837 (48.4%) were up-regulated in cases. In particular, genes participating to the smooth muscle contraction biological function were mostly up-regulated. Functional analysis revealed a significant enrichment of neuronal/muscular and neuronal/immunity processes. Upstream regulatory analysis of 180 genes involved in these processes suggested TLR4 and IL18 as critical key-players. Two functional gene networks were significantly over-represented: one involved in organ morphology, skeletal muscle system development and function, and neurological diseases, and the other participating in cell morphology, humoral immune response and cellular movement. These results highlight on pivotal genes that may play critical roles in neuronal/muscular and neuronal/immunity processes, and that may contribute to the onset and development of achalasia.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980661/
_version_	1613625453573046272

Gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia

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