Deficiency of Protein Tyrosine Phosphatase Non-Receptor Type 2 in Intestinal Epithelial Cells Has No Appreciable Impact on Dextran Sulphate Sodium Colitis Severity But Promotes Wound Healing.
OBJECTIVE
The protein tyrosine phosphatase non-receptor type 2 (PTPN2) is known to mediate susceptibility to inflammatory bowel diseases. Cell culture experiments suggest that PTPN2 influences barrier function, autophagy and secretion of pro-inflammatory cytokines. PTPN2 knockout mice die a few weeks after birth due to systemic inflammation, emphasizing the importance of this phosphatase in inflammatory processes. The aim of this study was to investigate the role of PTPN2 in colon epithelial cells by performing dextran sulphate sodium (DSS)-induced colitis in PTPN2xVilCre mice.


METHODS
Acute colitis was induced by administering 2.5 or 2% DSS for 7 days and chronic colitis by 4 cycles of treatment using 1% DSS. Body weight of mice was measured regularly and colonoscopy was done at the end of the experiments. Mice were sacrificed afterwards and colon specimens were obtained for H&amp;E staining. For analysis of wound healing, mechanical wounds were introduced during endoscopy and wound closure assessed by daily colonoscopy.


RESULTS
Although colonoscopy and weight development suggested changes in colitis severity, the lack of any influence of PTPN2 deficiency on histological scoring for inflammation severity after acute or chronic DSS colitis indicates that colitis severity is not influenced by epithelial-specific loss of PTPN2. Chronic colitis induced the development of aberrant crypt foci more frequently in PTPN2xVilCre mice compared to their wild type littermates. On the other hand, loss of PTPN2-induced enhanced epithelial cell proliferation and promoted wound closure.


CONCLUSIONS
Loss of PTPN2 in intestinal epithelial cells (IECs) has no significant influence on inflammation in DSS colitis. Obviously, loss of PTPN2 in IECs can be compensated in vivo, thereby suppressing a phenotype. This lack of a colitis-phenotype might be due to enhanced epithelial cell proliferation and subsequent increased wound-healing capacity of the epithelial layer.
Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
Stephanie H
SH
Kasper
Marianne R
MR
Spalinger
Irina
I
Leonardi
Alexandra
A
Gerstgrasser
Tina
T
Raselli
Claudia
C
Gottier
Kirstin
K
Atrott
Isabelle
I
Frey-Wagner
Anne
A
Fischbeck-Terhalle
Gerhard
G
Rogler
Michael
M
Scharl
D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000473:pathology; D003113:Colonoscopy; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D055786:Gene Knockout Techniques; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics*
D016264:Dextran Sulfate; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; C516653:Ptpn2 protein, mouse