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http://purl.uniprot.org/citations/36611909http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36611909http://www.w3.org/2000/01/rdf-schema#comment"

Background & aims

Celiac disease (CeD) is an immune-mediated enteropathy triggered in genetically susceptible (HLA-DQ2/8) individuals by a group of wheat proteins and related prolamins from cereals. The celiac intestine is characterized by an inversion of the differentiation/proliferation program of the enterocytes, with an increase in the proliferative compartment and crypt hyperplasia, which are the mechanisms that regulate the increased proliferation in CeD that arenot completely understood.The aim of this study is to understand the role of Protein Tyrosine Phosphatase Receptor Type K (PTPRK), a nodal phosphatase that regulates EGFR activation in the proliferation of the enterocytes from CeD biopsies and organoids.

Methods

The levels of PTPRK were evaluated by RT PCR, western blot (WB) and immunofluorescence techniques in intestinal biopsies and organoids from CeD patients and controls. Additionally, pEGFR and pERK were evaluated by WB and proliferation by BrdU incorporation. PTPRK si-RNA was silenced in CTR organoids and was overexpressed in CeD organoids.

Results

PTPRK was reduced in Gluten Containing Diet-Celiac Disease (GCD-CeD) and Potential-Celiac Disease(Pot-CeD) biopsies (p < 0.01-p < 0.05) whereas pEGFR (p < 0.01 p < 0.01), pERK (p < 0.01 p < 0.01) and proliferation were increased. (p < 0.05 p < 0.05) respect to the controls.The CeD organoids reproduced these same alterations. Silencing of PTPRK in CTR organoids increased pEGFR, pERK and proliferation. The overexpression of PTPRK in CeD organoids reduced pEGFR, pERK and proliferation.

Conclusions

modulation of PTPRK levels can reduce or increase pEGFR, pERK and proliferation in CeD or CTR organoids, respectively. The CeD organoids can be a good model to study the mechanisms of the disease."xsd:string
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http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/author"Barone M.V."xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/author"Nicoletti M."xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/author"Porpora M."xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/author"Lania G."xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/author"Auricchio S."xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/author"Bellomo C."xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/author"Maglio M."xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/author"Nanayakkara M."xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/author"Marano A."xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/author"Furone F."xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/name"Cells"xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/pages"115"xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/title"PTPRK, an EGFR Phosphatase, Is Decreased in CeD Biopsies and Intestinal Organoids."xsd:string
http://purl.uniprot.org/citations/36611909http://purl.uniprot.org/core/volume"12"xsd:string
http://purl.uniprot.org/citations/36611909http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36611909
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