Role of Growth Factors in Gastric Tissue Homeostasis
There are several key growth factors and morphogens that have been identified as critical regulators of gastric epithelial cell homeostasis. Our lab has previously demonstrated, via a gastrin-null mouse, that gastrin is a critical regulator of parietal cell function and gastric gland homeostasis. Through microarray analysis of gastrin-null mice, we also identified Parathyroid Hormone Like Hormone (Pthlh) as a potentially new gastric growth factor. Current studies seek to identify the gastric localization of Pthlh, as well as its potential role in regulation of gastric epithelial cell function. Experimental tools use the Pthlh-lacZ reporter mouse, gastrin-null mice, and human gastric cancer cell lines.
Hip1r is a clathrin binding protein involved in membrane endocytosis. Hip1r knockout mice display a parietal cell defect due to the inability to reform the canilicular membrane. This defect leads to apoptosis of the parietal cells and remodeling of the gastric mucosa, eventually resulting in antral tumors. Current studies in the lab entail analysis of the inflammatory components involved in the mucosal remodeling process.
Human patients sustained on total parenteral nutrition (TPN) due to gastrointestinal dysfunction display atrophy of the intestinal epithelium. Current studies in the lab involve the analysis of the GI tract of mice that have undergone TPN administration, specifically examining morphological and growth factor changes.