Peptidoglycan recognition protein 3 (Pglyrp3) is associated with intestinal mucosal homeostasis and protection against colitis (67.12)

Abstract

Abstract Peptidoglycan recognition protein 3 (Pglyrp3) is a bactericidal protein expressed in the epithelial cells of tongue, esophagus, stomach and intestine. Pglyrp3-deficient mice compared to wild type (WT) mice have increased sensitivity to dextran sodium sulfate (DSS)-induced colitis. The increased colitis is characterized by loss of epithelial cells, severe hyperplasia of the lamina propria and ulcers. The aim of this study was to determine whether Pglyrp3 plays a role in maintaining intestinal epithelial integrity by regulating proliferation and apoptosis of epithelial cells. We report that Pglyrp3-deficient mice treated with DSS have significantly higher TUNEL positive cells, increased Annexin V staining and higher levels of cleaved caspase 3 in the epithelial cells of the colon compared to WT mice. The number of bromodeoxyuridine (BrdU) positive cells, which indicates proliferating cells, is significantly lower in Pglyrp3-deficient mice compared to WT mice. Serum levels of FITC-dextran are significantly higher in DSS-treated Pglyrp3-deficient compared to WT mice, which indicates an increased loss of epithelial lining and loss of barrier function in Pglyrp3-deficient mice. Our results indicate that Pglyrp3 is important in maintaining the epithelial lining of the colon and loss of this protein results in increased apoptosis, decreased proliferation and increased loss of barrier function, which are important contributing factors to increased colitis in Pglyrp3-deficient mice.