St Petersburg University researchers reveal the mechanism of radiation-induced intestinal barrier damage

Exposure to ionising radiation (IR), associated with nuclear power plant accidents and long-duration space flights, can cause severe damage to cells of the body. Exposure to this type of radiation, however, is commonly used in the treatment of oncological diseases. In radiotherapy used for cancer treatment, radiation may affect not only the area of the body where the tumor is located, but also surrounding healthy tissues and organs.

The research findings are published in the International Journal of Molecular Sciences.

One of the consequences of exposure to ionising radiation on healthy cells is the gastrointestinal acute radiation syndrome. To study how different parts of the intestine respond to ionising radiation, the researchers conduct experiments on model animals. This enables them to find common and specific molecular mechanisms of intestinal barrier dysfunction first in animals and eventually in humans. 

In experiments on rats, the researchers from St Petersburg University focused on studying key proteins that form channels that make it possible for certain molecules to pass through intercellular tight junctions in the intestine and regulate paracellular transport through them. It is intestinal epithelial cells that provide a barrier to protect the intestine against harmful substances and pathogens. 

St Petersburg University physiologists have studied claudin proteins. Various combinations and changes in the level of claudins lead to changes in the barrier properties of the epithelium. According to the University researchers, IR-induced overexpression of some claudins indicates increased intestinal permeability, while the presence of other claudins may signal adaptive processes in cells. In-depth understanding of these correlations enabled the researchers to reveal the mechanism of IR-induced intestinal barrier dysfunction, which in future may be a critical factor in the choice of cancer therapy.

We obtained priority data on the nature and mosaic of change in claudin proteins in different segments of the intestine and were able to show their sensitivity to ionising radiation. The main research findings highlight the damaging effects of ionising radiation on the key regulator of the intestinal barrier properties, the so-called claudin-2.

Igor Krivoi and Aleksandr Markov, Professors in the Department of General Physiology at St Petersburg University

This study is a continuation of the research titled "Molecular diversity and functional Na,K-ATPase and claudins interaction", conducted by a team of St Petersburg University researchers, who won the University’s award for the best research work in the category "For Fundamental Achievements in Science". 

Na,K-ATPase, also known as the sodium-potassium pump, is a type of transport protein found in the plasma membrane of animal cells. It performs several important functions, playing a vital role in all living cells. In addition to its "classical" role of ion transporter, when exposed to ouabain — a plant-derived compound, the Na,K-ATPase can activate a number of signalling pathways in neuronal, muscle and epithelial cells. 

"Changes in ouabain concentrations and initiated intercellular signalling have important adaptive significance for tissues, organs, and the whole body in a variety of physiological and pathophysiological conditions, which is manifested in neuroprotective, anticancer and antiviral effects. In the study, for the first time in the conditions of radiation injury in rat model, we used ouabain injections to increase concentration of circulating ouabain in the blood. Our findings revealed the protective effect of this exposure on claudin-2 and barrier properties of the intestinal epithelium," the researchers stressed. 

In the study, the St Petersburg University researchers proposed a hypothetical scheme of the molecular mechanism of the protective effect of ouabain exposure. The research findings could potentially be used for the development of new measures to prevent and correct inflammatory bowel disease and other intestinal disorders, including health problems associated with exposure to radiation in clinical practice, and during long-duration space missions.