{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:51:45Z","timestamp":1779310305018,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T00:00:00Z","timestamp":1523404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP15171"],"award-info":[{"award-number":["GGP15171"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005969","name":"Universit\u00e0 di Bologna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005969","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004740","name":"Fondazione del Monte di Bologna e Ravenna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004740","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2018,9]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC<\/jats:styled-content>) abnormalities leading to deranged\/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC<\/jats:styled-content> changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia.<\/jats:p><\/jats:sec>Methods<\/jats:title>Esophageal full\u2010thickness biopsies from 42 (22 females; age range: 16\u201082\u00a0years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA<\/jats:styled-content> extracted from biopsies of cases and controls was used for library preparation and sequencing. Data analysis was performed with the \u201cedgeR\u201d option of R\u2010Bioconductor. Data were validated by real\u2010time RT<\/jats:styled-content>\u2010PCR<\/jats:styled-content>, western blotting and immunohistochemistry.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Quantitative transcriptome evaluation and cluster analysis revealed 111 differentially expressed genes, with a P\u00a0<\/jats:italic>\u2264\u00a010\u22123<\/jats:sup>. Nine genes with a P\u00a0<\/jats:italic>\u2264\u00a010\u22124<\/jats:sup> were further validated. CYR<\/jats:styled-content>61<\/jats:italic>, CTGF<\/jats:styled-content><\/jats:italic>, c\u2010KIT<\/jats:styled-content><\/jats:italic>, DUSP<\/jats:styled-content>5<\/jats:italic>, EGR<\/jats:styled-content>1<\/jats:italic> were downregulated, whereas AKAP<\/jats:styled-content>6<\/jats:italic> and INPP<\/jats:styled-content>4B<\/jats:italic> were upregulated in patients vs controls. Compared to controls, immunohistochemical analysis revealed a clear increase in INPP<\/jats:styled-content>4B, whereas c\u2010KIT<\/jats:styled-content> immunolabeling resulted downregulated. As INPP<\/jats:styled-content>4B regulates Akt pathway, we used western blot to show that phospho\u2010Akt was significantly reduced in achalasia patients vs controls.<\/jats:p><\/jats:sec>Conclusions & Inferences<\/jats:title>The identification of altered gene expression, including INPP<\/jats:styled-content>4B<\/jats:italic>, a regulator of the Akt pathway, highlights novel signaling pathways involved in the neuronal and ICC<\/jats:styled-content> changes underlying primary achalasia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13346","type":"journal-article","created":{"date-parts":[[2018,4,12]],"date-time":"2018-04-12T02:13:49Z","timestamp":1523499229000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["INPP<\/scp>4B<\/i> overexpression and c\u2010KIT<\/scp><\/i> downregulation in human achalasia"],"prefix":"10.1111","volume":"30","author":[{"given":"E.","family":"Bonora","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences DIMEC University of Bologna and St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Bianco","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences DIMEC University of Bologna and St. Orsola\u2010Malpighi Hospital Bologna Italy"},{"name":"Department of Medical and Veterinary Sciences DIMEVET University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Stanzani","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences DIMEC University of Bologna and St. Orsola\u2010Malpighi Hospital Bologna Italy"},{"name":"Department of Medical and Veterinary Sciences DIMEVET University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Giancola","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences DIMEC University of Bologna and St. Orsola\u2010Malpighi Hospital Bologna Italy"},{"name":"Department of Medical and Veterinary Sciences DIMEVET University of Bologna Bologna Italy"},{"name":"Centro di Ricerca Biomedica Applicata St.Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Astolfi","sequence":"additional","affiliation":[{"name":"Interdepartmental Center for Cancer Research \u201cG. 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M.","family":"Martelli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine DIMES University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Boschetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences DIMEC University of Bologna and St. Orsola\u2010Malpighi Hospital Bologna Italy"},{"name":"Centro di Ricerca Biomedica Applicata St.Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Lugaresi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences DIMEC University of Bologna and St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Ioannou","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences DIMEC University of Bologna and St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Torresan","sequence":"additional","affiliation":[{"name":"Department of Digestive System St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Stanghellini","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences DIMEC University of Bologna and St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Clavenzani","sequence":"additional","affiliation":[{"name":"Department of Medical and Veterinary Sciences DIMEVET University of Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Seri","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences DIMEC University of Bologna and St. Orsola\u2010Malpighi Hospital Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Moonen","sequence":"additional","affiliation":[{"name":"Translational Research in GastroIntestinal Disorders (TARGID) Department of Clinical and Experimental Medicine KU Leuven University Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Van Beek","sequence":"additional","affiliation":[{"name":"Translational Research in GastroIntestinal Disorders (TARGID) Department of Clinical and Experimental Medicine KU Leuven University Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Wouters","sequence":"additional","affiliation":[{"name":"Translational Research in GastroIntestinal Disorders (TARGID) Department of Clinical and Experimental Medicine KU Leuven University Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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