2025-06-06 カリフォルニア大学リバーサイド校 (UCR)
<関連情報>
- https://news.ucr.edu/articles/2025/06/06/genetic-link-found-between-iron-deficiency-crohns-disease
- https://www.mdpi.com/1422-0067/26/7/3356
PTPN2は炎症性腸疾患患者の鉄ハンドリングタンパク質の発現を制御し、マウスの鉄欠乏を予防する PTPN2 Regulates Iron Handling Protein Expression in Inflammatory Bowel Disease Patients and Prevents Iron Deficiency in Mice
Hillmin Lei,Ali Shawki,Alina N. Santos,Vinicius Canale,Salomon Manz,Meli’sa S. Crawford,Pritha Chatterjee,Marianne R. Spalinger,,Michael Scharl and Declan F. McCole
International Journal of Molecular Sciences Published: 3 April 2025
DOI:https://doi.org/10.3390/ijms26073356
Abstract
Anemia is the most common extraintestinal manifestation of inflammatory bowel disease (IBD). Iron deficiency is the most frequent cause of anemia in IBD; however, the mechanisms involved are still poorly understood. Here, we investigated the role of the IBD risk gene, protein tyrosine phosphatase non-receptor type 2 (PTPN2), in regulating iron homeostasis. Proteomic analyses were performed on serum from IBD patients genotyped for the IBD-associated loss-of-function rs1893217 PTPN2 variant. Constitutive Ptpn2 wild type (WT), heterozygous (Het), and knockout (KO) mice were analyzed for iron content, blood parameters, and expression of iron handling proteins. Iron absorption was assessed through radiotracer assays. Serum proteomic analyses revealed that the “iron homeostasis signaling pathway” was the main pathway downregulated in Crohn’s disease (CD) patients carrying the PTPN2 risk allele, independent of disease activity. Ptpn2-KO mice showed characteristics of anemia, including reduced hemoglobin concentrations along with serum and tissue iron deficiency and elevated serum hepcidin levels vs. Ptpn2-WT and Het mice. 55Fe absorption via oral gavage was significantly impaired in Ptpn2-KO mice. Correspondingly, Ptpn2-KO mice showed reduced apical membrane expression of the iron transporter DMT1. CD patients with the PTPN2 loss-of-function rs1893217 variant display alterations in serum iron handling proteins. Loss of Ptpn2 in mice caused features of anemia, including iron deficiency associated with reduced apical membrane expression of DMT1. These findings identify an important role for PTPN2 in regulating systemic iron homeostasis.
