Role of the G Protein-coupled Receptor Lgr4 in Inflammatory Bowel Syndrome♦
Lgr4 Gene Deficiency Increases Susceptibility and Severity of Dextran Sodium Sulfate-induced Inflammatory Bowel Disease in Mice
♦ See referenced article, J. Biol. Chem. 2013, 288, 8794–8803
Inflammatory bowel syndrome is the catchall phrase to describe inflammation of the intestine and colon. Intestinal epithelial cells, the proliferation and differentiation of which are based predominantly on Wnt/β-catenin signaling, are affected by the syndrome. However, not much is understood about how the Wnt/β-catenin pathway goes awry during intestinal inflammation. In this Paper of the Week, a team led by Dali Li and Mingyao Liu at the East China Normal University established that a G protein-coupled receptor called Lgr4 or GPR48 is critical for modulating the Wnt/β-catenin pathway to maintain the homeostasis and integrity of the intestinal epithelial cell barrier. The investigators demonstrated that mice missing Lgr4 were highly susceptible to intestinal inflammation, but when Wnt/β-catenin signaling was reactivated by either genetic or chemical means, the inflammation in the Lgr4 mutant mice was greatly reduced. The authors concluded, “The identification of the essential roles of Lgr4 in inflammatory bowel disease represents an advance that has implications for diagnosis or potential drug targets for human colitis.”
Severe intestinal inflammation in Lgr4−/− mice. Scale bars = 50 μm.
Role of the G Protein-coupled Receptor Lgr4 in Inflammatory Bowel Syndrome♦
Shijie Liu
Current position: Ph.D. Student, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Education: Master's in Genetics, 2009, College of Life Science, Hunan Normal University, Changsha, China
Nonscientific interests: Sports, music, and travel
During the first three years of my master's degree research, I began learning how to perform scientific studies on gene functions involved in heart development. With experience in molecular biology and rodent model organisms, I joined Mingyao Liu's lab and started work with Dali Li on G protein-coupled receptor (GPCR) signaling in adult stem cells, tissue regeneration, and tumors using intestinal epithelium as a model. GPCRs represent a large family of transmembrane receptors that play broad roles in development and disease and are good drug targets. Thus, understanding the physiological functions of distinct GPCRs is very important not only for fundamental research but also for human health.
Inflammatory bowel disease (IBD), the collective term for Crohn disease and ulcerative colitis, is a common inflammatory disorder of the human gastrointestinal tract. The focus of this work was to determine the function and mechanisms of Lgr4 (leucine-rich repeat-containing G protein-coupled receptor 4) in IBD in mice. Our findings revealed that lost of Lgr4 in mice resulted in increased susceptibility to dextran sulfate sodium-induced IBD. This study demonstrated that Lgr4 regulates intestinal homeostasis and regeneration through Wnt/β-catenin signaling, further supporting Lgr4 as one of the receptors for R-spondins, the Wnt amplifiers.
Read Liu's article on page 8794.