Osmotic pressure: the secret of cell growth and immune response

This study of mice is the first to present evidence that a transcription factor that turns on gene expression is important for the normal proliferation of cells in a certain osmotic environment and is necessary for the body to produce an immune response to an invading pathogen.

Osmotic pressure is produced when the molecular concentrations of the internal and external environments of the cells are different. In this case, moisture flows into or out of the cells through the permeation, thereby changing the internal environment of the cells. High osmotic pressure forces water to diffuse out of the cell, causing the cell to contract, which can destroy DNA and proteins, stagnant cell cycles, and ultimately cell death. Cells respond to changes in osmotic pressure by activating the osmotic response pathway. This pathway is controlled by a gene called NFAT5 (nuclear factor of activated T cells 5)/TonEBP (tonicity enhancer binding protein). The NFAT5/TonEBP protein is the only mammalian transcription factor known to be activated by high osmotic pressure.

Ho said in his work in the narrative group that the kidney was previously the only tissue in the body that was affected by osmotic pressure: the kidney controls the amount of water and salt in the blood through a mechanism that causes the osmotic pressure in the local area of ​​the kidney to be very high. .

"As an immunologist, we find it quite doubtful when we find a protein that helps kidney cells adapt to osmotic pressure in the immune system," Ho said. "Because there was no evidence that the immune system cells or cells outside the kidneys were significantly affected by osmotic pressure."

One of the difficulties in studying the stress on cells in the body is that it is almost impossible to accurately reproduce the complexity of a tissue with a special microenvironment in a living state in the laboratory. To study osmotic pressure, the team constructed a mouse that did not express NFAT5/TonEBP. They found that the mouse immune system was damaged and that mouse cells could not grow in the presence of osmotic pressure.

"We now believe that cell proliferation processes in a tissue microenvironment are exposed to osmotic pressure," Ho said. "If a cell can't adapt to osmotic pressure, then it can't grow. The immune system relies especially on this osmotic pressure reaction, because in order to successfully resist the invasion of viruses or bacteria, the cells of the immune system must proliferate rapidly."

Dr. Steffan N. Ho, assistant professor of pathology at UCSD and the first author of the article, pointed out that these new findings have brought new hopes for the development of drugs for autoimmune diseases, transplant rejection and cancer.

“What is especially exciting for us is the significance of these findings for cancer cell biology. Because the growth of malignant cells cannot be regulated, the blood vessels and lymphatic vessels in the tumor cannot grow normally, which may affect the osmotic pressure, so the tissue of the tumor is slightly The environment is very unique. If the growth of cancer cells in the body must have an adaptation to osmotic pressure, then this stress response pathway will become a new target for the identification of anticancer drugs."

These studies were funded by the National Center for Health, and the core equipment used in the study was provided by the National Cancer Center.