Digestive and Renal Research

Digestive diseases can be caused by many factors, including genetic predisposition, infection, inflammation, and lifestyle choices. Common digestive disorders include ulcerative colitis (UC), Crohn's disease (CD), and irritable bowel syndrome. Some common renal diseases include chronic kidney disease, polycystic kidney disease, and glomerulonephritis. Although digestive and renal diseases can be severe, a growing body of research is beginning to understand these conditions and how to treat them. In many cases, early diagnosis and treatment can improve the prognosis for patients suffering from these diseases. As such, Digestive and Renal Research is essential for developing new treatments and improving the quality of life for patients with these conditions.

• Crohn's disease (CD)

CD is a chronic inflammatory bowel disease affecting the digestive tract lining. The cause of CD is unknown, but it is thought to involve a combination of genetic and environmental factors. There is no cure for CD, but treatments can help to control the symptoms. The mainstay of treatment for CD is anti-inflammatory medication, which can have limited effectiveness.

• Chronic Kidney Disease (CKD)

CKD is a type of kidney disease in which there is a gradual loss of kidney function over months to years. Initially, there are generally no symptoms; later, symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Causes of CKD include diabetes, high blood pressure, glomerulonephritis, and polycystic kidney disease. Risk factors include a family history of CKD.

• Polycystic Kidney Disease (PKD)

PKD is a condition that results in the formation of cysts in the kidneys. These cysts can cause the kidneys to enlarge and lead to kidney failure. PKD is a hereditary condition, and there is currently no cure. However, researchers are exploring new treatments that target membrane proteins to improve the symptoms of PKD.

Membrane Proteins in Digestive and Renal Research

Membrane proteins play an essential role in digestive and renal function. They also target many drugs used to treat digestive and renal diseases. Because of their importance, researchers want to better understand how membrane proteins work. They are embedded in cell membranes, making them hard to reach and explore. Additionally, they often interact with other proteins, making it difficult to isolate their individual effects. Despite these challenges, researchers have made significant progress in understanding how membrane proteins work. This knowledge is helping to develop new treatments for digestive and renal diseases.

• Leucine-rich Repeat-containing G-protein Coupled Receptor 5 (LGR5)

LGR5 is a protein that is involved in the regulation of cell proliferation, differentiation, and death. In digestive and renal diseases, there is an abnormal proliferation of cells, leading to tumors forming. The targeting of LGR5 with drugs may help to stop the progression of these diseases. This could potentially lead to better outcomes for patients and reduced costs for the healthcare system.

Fig.1 Epithelial stem cells compartments in the mammalian intestine and Wnt signaling. (Andrea, et al., 2009)

• A2A Receptor

The A2A receptor is a G protein-coupled receptor widely distributed in the digestive system, including the stomach, intestine, and kidney. A2A receptor is known to be involved in the regulation of digestive tract motility and kidney function. Recently, the A2A receptor has been targeted to treat chronic digestive and renal diseases. Several drugs that target the A2A receptor have been developed, and clinical trials are currently underway to evaluate their efficacy in treating these conditions.

Fig.2 Mechanism of signal transduction of A2A Receptors. (Boknik, et al., 2021)

• Polycystin-1

This protein is found in the cell membranes of kidney cells and plays a role in regulating cell growth. Mutations in the polycystin-1 gene are thought to be responsible for the development of PKD. By targeting polycystin-1 with drugs, researchers hope to control cell growth and prevent the formation of cysts.

• Fibroblast Growth Factor 23 (FGF23)

FGF23 is produced by the kidney in response to changes in calcium levels, and it acts to regulate phosphorus and vitamin D metabolism. In CKD, however, FGF23 production becomes dysregulated, accumulating the protein in the bloodstream. This, in turn, can cause abnormalities in bone mineralization and calcium homeostasis, ultimately leading to CKD progression. One potential treatment for CKD is targeting FGF23 with antibodies. Antibodies are proteins that can bind to specific targets, such as FGF23, and prevent them from performing their normal functions.

Fig.3 The regulation and action of FGF23. (Emmett, 2008)

References

1. Andrea, H.; et al. Wnt signaling, Lgr5, and Stem Cells in the Intestine and Skin. The American Journal of Pathology. 2009, 174(3): 715-721.
2. Boknik, P.; et al. Role of Cardiac A2A Receptors Under Normal and Pathophysiological Conditions. Frontiers in Pharmacology. 2021, 11: 627838.
3. Emmett, M. What does serum fibroblast growth factor 23 do in hemodialysis patients. Kidney International. 2008, 73(1): 3-5.