ANGPTL2 controls intestinal homeostasis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H06508
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Kumamoto University
• Principal Investigator: Horiguchi Haruki 熊本大学, 生命資源研究・支援センター, 特定事業研究員 (70755454)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: 潰瘍性大腸炎 / アンジオポエチン様2

Outline of Final Research Achievements

We assessed ANGPTL2 function in intestinal physiology and disease in vivo. Although intestinal development proceeded normally in Angptl2-deficient mice, expression levels of the intestinal stem cell (ISC) marker gene Lgr5 decreased, which was associated with decreased transcriptional activity of β-catenin in Angptl2-deficient mice. Epithelial regeneration after injury was significantly impaired in Angptl2-deficient relative to wild-type mice. ANGPTL2 was expressed and functioned within the mesenchymal compartment cells known as intestinal subepithelial myofibroblasts (ISEMFs). ANGPTL2 derived from ISEMFs maintained the intestinal stem cell niche by modulating levels of competing signaling between bone morphogenetic protein (BMP) and β-catenin. These results support the importance of ANGPTL2 in the stem cell niche in regulating stemness and epithelial wound healing in the intestine.

Free Research Field

分子細胞生物学