PMID- 36611909
OWN - NLM
STAT- MEDLINE
DCOM- 20230110
LR  - 20230205
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Dec 28
TI  - PTPRK, an EGFR Phosphatase, Is Decreased in CeD Biopsies and Intestinal 
      Organoids.
LID - 10.3390/cells12010115 [doi]
LID - 115
AB  - 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.
FAU - Nanayakkara, Merlin
AU  - Nanayakkara M
AUID- ORCID: 0000-0002-2569-4606
AD  - Department of Translational Medical Science, Section of Pediatrics, University 
      Federico II, Via S. Pansini 5, 80131 Naples, Italy.
FAU - Bellomo, Claudia
AU  - Bellomo C
AD  - Department of Translational Medical Science, Section of Pediatrics, University 
      Federico II, Via S. Pansini 5, 80131 Naples, Italy.
FAU - Furone, Francesca
AU  - Furone F
AD  - Department of Translational Medical Science, Section of Pediatrics, University 
      Federico II, Via S. Pansini 5, 80131 Naples, Italy.
FAU - Maglio, Mariantonia
AU  - Maglio M
AD  - ELFID (European Laboratory for the Investigation of Food Induced Diseases), 
      University Federico II, Via S. Pansini 5, 80131 Naples, Italy.
FAU - Marano, Antonella
AU  - Marano A
AD  - ELFID (European Laboratory for the Investigation of Food Induced Diseases), 
      University Federico II, Via S. Pansini 5, 80131 Naples, Italy.
FAU - Lania, Giuliana
AU  - Lania G
AD  - ELFID (European Laboratory for the Investigation of Food Induced Diseases), 
      University Federico II, Via S. Pansini 5, 80131 Naples, Italy.
FAU - Porpora, Monia
AU  - Porpora M
AD  - ELFID (European Laboratory for the Investigation of Food Induced Diseases), 
      University Federico II, Via S. Pansini 5, 80131 Naples, Italy.
FAU - Nicoletti, Martina
AU  - Nicoletti M
AD  - Department of Translational Medical Science, Section of Pediatrics, University 
      Federico II, Via S. Pansini 5, 80131 Naples, Italy.
FAU - Auricchio, Salvatore
AU  - Auricchio S
AD  - ELFID (European Laboratory for the Investigation of Food Induced Diseases), 
      University Federico II, Via S. Pansini 5, 80131 Naples, Italy.
FAU - Barone, Maria Vittoria
AU  - Barone MV
AUID- ORCID: 0000-0001-6190-4917
AD  - Department of Translational Medical Science, Section of Pediatrics, University 
      Federico II, Via S. Pansini 5, 80131 Naples, Italy.
AD  - ELFID (European Laboratory for the Investigation of Food Induced Diseases), 
      University Federico II, Via S. Pansini 5, 80131 Naples, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221228
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.1.3.48 (PTPRK protein, human)
RN  - EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 2)
RN  - EC 2.7.10.1 (EGFR protein, human)
SB  - IM
MH  - Humans
MH  - *Celiac Disease/genetics/metabolism
MH  - ErbB Receptors/metabolism
MH  - Enterocytes/metabolism
MH  - Biopsy
MH  - Genetic Predisposition to Disease
MH  - Receptor-Like Protein Tyrosine Phosphatases, Class 2/metabolism
PMC - PMC9818839
OTO - NOTNLM
OT  - EGFR
OT  - PTPRK
OT  - celiac disease
OT  - intestinal organoids
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/09 06:00
MHDA- 2023/01/11 06:00
PMCR- 2022/12/28
CRDT- 2023/01/08 01:06
PHST- 2022/11/07 00:00 [received]
PHST- 2022/12/12 00:00 [revised]
PHST- 2022/12/21 00:00 [accepted]
PHST- 2023/01/08 01:06 [entrez]
PHST- 2023/01/09 06:00 [pubmed]
PHST- 2023/01/11 06:00 [medline]
PHST- 2022/12/28 00:00 [pmc-release]
AID - cells12010115 [pii]
AID - cells-12-00115 [pii]
AID - 10.3390/cells12010115 [doi]
PST - epublish
SO  - Cells. 2022 Dec 28;12(1):115. doi: 10.3390/cells12010115.