PTPRK, an EGFR Phosphatase, Is Decreased in CeD Biopsies and Intestinal Organoids

Merlin Nanayakkara; Claudia Bellomo; Francesca Furone; Mariantonia Maglio; Antonella Marano; Giuliana Lania; Monia Porpora; Martina Nicoletti; Salvatore Auricchio; Maria Vittoria Barone

doi:10.3390/cells12010115

PTPRK, an EGFR Phosphatase, Is Decreased in CeD Biopsies and Intestinal Organoids

Cells. 2022 Dec 28;12(1):115. doi: 10.3390/cells12010115.

Affiliations

¹ Department of Translational Medical Science, Section of Pediatrics, University Federico II, Via S. Pansini 5, 80131 Naples, Italy.
² ELFID (European Laboratory for the Investigation of Food Induced Diseases), University Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Abstract

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.

Keywords: EGFR; PTPRK; celiac disease; intestinal organoids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biopsy
Celiac Disease* / genetics
Celiac Disease* / metabolism
Enterocytes / metabolism
ErbB Receptors / metabolism
Genetic Predisposition to Disease
Humans
Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism

Substances

ErbB Receptors
PTPRK protein, human
Receptor-Like Protein Tyrosine Phosphatases, Class 2
EGFR protein, human

Grants and funding

Project funded under the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3—Call for proposals No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union—NextGenerationEU; Award Number: Project code PE00000003, Concession Decree No. 1550 of 11 October 2022 adopted by the Italian Ministry of University and Research, CUP D93C22000890001, Project title “ON Foods—Research and innovation network on food and nutrition Sustainability, Safety and Security—Working ON Foods”.