BACKGROUND/AIMS: Knockdown of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) exaggerates IFN-γ-induced intestinal barrier defects, but mice constitutively lacking PTPN2 in epithelial cells (PTPN2xVilCre mice) do not show changes in epithelial function or enhanced susceptibility to experimental colitis. Here, we investigated whether PTPN2 modulates the expression of related tyrosine phosphatases. METHODS: PTPN2 knockdown in HT-29 cells was induced using siRNA constructs. Acute colitis in PTPN2xVilCre mice was induced by 2% dextran sulfate sodium (DSS) in drinking water for 7 days. Colitis-associated tumors were induced by injection of azoxymethane prior to treatment with DSS for 3 consecutive cycles. RESULTS: In HT-29 cells, PTPN2 depletion resulted in enhanced mRNA expression of PTPN11 and PTPN23 and in parallel to upregulation of IL-18 mRNA upon treatment with TNF for 24 h. DSS treatment of PTPN2-deficient mice resulted in a strong induction of Ptpn23 mRNA in colon tissue in vivo. In the tumor model, Ptpn23 mRNA was again clearly upregulated in nontumor tissue from PTPN2-deficient mice; however, this was not observed in tumor tissue. CONCLUSIONS: Our experiments show that PTPN23 function might, at least partially, compensate lack of PTPN2 in epithelial cells. Upregulation of PTPN23 might therefore crucially contribute to the lack of a colitis phenotype in PTPN2-VilCre mice.
BACKGROUND/AIMS: Knockdown of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) exaggerates IFN-γ-induced intestinal barrier defects, but mice constitutively lacking PTPN2 in epithelial cells (PTPN2xVilCre mice) do not show changes in epithelial function or enhanced susceptibility to experimental colitis. Here, we investigated whether PTPN2 modulates the expression of related tyrosine phosphatases. METHODS: PTPN2 knockdown in HT-29 cells was induced using siRNA constructs. Acute colitis in PTPN2xVilCre mice was induced by 2% dextran sulfate sodium (DSS) in drinking water for 7 days. Colitis-associated tumors were induced by injection of azoxymethane prior to treatment with DSS for 3 consecutive cycles. RESULTS: In HT-29 cells, PTPN2 depletion resulted in enhanced mRNA expression of PTPN11 and PTPN23 and in parallel to upregulation of IL-18 mRNA upon treatment with TNF for 24 h. DSS treatment of PTPN2-deficient mice resulted in a strong induction of Ptpn23 mRNA in colon tissue in vivo. In the tumor model, Ptpn23 mRNA was again clearly upregulated in nontumor tissue from PTPN2-deficient mice; however, this was not observed in tumor tissue. CONCLUSIONS: Our experiments show that PTPN23 function might, at least partially, compensate lack of PTPN2 in epithelial cells. Upregulation of PTPN23 might therefore crucially contribute to the lack of a colitis phenotype in PTPN2-VilCre mice.
Entities:
Keywords:
HD-PTP; Intestinal epithelial cells; Intestinal inflammation; T cell protein tyrosine phosphatase; Tyrosine phosphatases
Authors: E Asante-Appiah; K Ball; K Bateman; K Skorey; R Friesen; C Desponts; P Payette; C Bayly; R Zamboni; G Scapin; C Ramachandran; B P Kennedy Journal: J Biol Chem Date: 2001-05-14 Impact factor: 5.157
Authors: Michael Scharl; Declan F McCole; Achim Weber; Stephan R Vavricka; Pascal Frei; Silvia Kellermeier; Theresa Pesch; Michael Fried; Gerhard Rogler Journal: Gut Date: 2010-11-29 Impact factor: 23.059
Authors: Yaya Wang; Iftach Shaked; Stephanie M Stanford; Wenbo Zhou; Julie M Curtsinger; Zbigniew Mikulski; Zachary R Shaheen; Genhong Cheng; Kristy Sawatzke; Amanda M Campbell; Jennifer L Auger; Hatice Bilgic; Fernanda M Shoyama; David O Schmeling; Henry H Balfour; Kiminori Hasegawa; Andrew C Chan; John A Corbett; Bryce A Binstadt; Matthew F Mescher; Klaus Ley; Nunzio Bottini; Erik J Peterson Journal: Immunity Date: 2013-07-18 Impact factor: 31.745
Authors: Marie-Claude Gingras; Dmitri Kharitidi; Valérie Chénard; Noriko Uetani; Maxime Bouchard; Michel L Tremblay; Arnim Pause Journal: Int J Dev Biol Date: 2009 Impact factor: 2.203
Authors: Michael Scharl; Gisela Paul; Achim Weber; Barbara C Jung; Michael J Docherty; Martin Hausmann; Gerhard Rogler; Kim E Barrett; Declan F McCole Journal: Gastroenterology Date: 2009-10-08 Impact factor: 22.682
Authors: Andre Franke; Dermot P B McGovern; Jeffrey C Barrett; Kai Wang; Graham L Radford-Smith; Tariq Ahmad; Charlie W Lees; Tobias Balschun; James Lee; Rebecca Roberts; Carl A Anderson; Joshua C Bis; Suzanne Bumpstead; David Ellinghaus; Eleonora M Festen; Michel Georges; Todd Green; Talin Haritunians; Luke Jostins; Anna Latiano; Christopher G Mathew; Grant W Montgomery; Natalie J Prescott; Soumya Raychaudhuri; Jerome I Rotter; Philip Schumm; Yashoda Sharma; Lisa A Simms; Kent D Taylor; David Whiteman; Cisca Wijmenga; Robert N Baldassano; Murray Barclay; Theodore M Bayless; Stephan Brand; Carsten Büning; Albert Cohen; Jean-Frederick Colombel; Mario Cottone; Laura Stronati; Ted Denson; Martine De Vos; Renata D'Inca; Marla Dubinsky; Cathryn Edwards; Tim Florin; Denis Franchimont; Richard Gearry; Jürgen Glas; Andre Van Gossum; Stephen L Guthery; Jonas Halfvarson; Hein W Verspaget; Jean-Pierre Hugot; Amir Karban; Debby Laukens; Ian Lawrance; Marc Lemann; Arie Levine; Cecile Libioulle; Edouard Louis; Craig Mowat; William Newman; Julián Panés; Anne Phillips; Deborah D Proctor; Miguel Regueiro; Richard Russell; Paul Rutgeerts; Jeremy Sanderson; Miquel Sans; Frank Seibold; A Hillary Steinhart; Pieter C F Stokkers; Leif Torkvist; Gerd Kullak-Ublick; David Wilson; Thomas Walters; Stephan R Targan; Steven R Brant; John D Rioux; Mauro D'Amato; Rinse K Weersma; Subra Kugathasan; Anne M Griffiths; John C Mansfield; Severine Vermeire; Richard H Duerr; Mark S Silverberg; Jack Satsangi; Stefan Schreiber; Judy H Cho; Vito Annese; Hakon Hakonarson; Mark J Daly; Miles Parkes Journal: Nat Genet Date: 2010-12 Impact factor: 38.330