Scientists from the Weizmann Institute discovered that analyzing the characteristics of the connective tissue, the uncontrolled cutting and fusion processes that occur in it, can help diagnose diseases - and that protecting the tissue can help slow down and even stop the rate of development of diseases
The connective tissue, which serves as a "case" for all the cells of the body and supports them, consists of an accumulation of protein molecules and fibers (collagen, gelatin and laminin). At first glance it may seem like a kind of "scaffolding", but in fact it plays a central role in the development and manifestation of diseases - from infections and inflammations to the flu and cancer. "Recognition of the diverse and central roles of this texture was established only recently," she says Prof. Irit Sagi From the Department of Biological Control at the Weizmann Institute of Science. "Now we understand that the connective tissue is a kind of 'warehouse' that stores controlled signals that affect the functioning of all body cells."
The interactions between the cells and the connective tissue are mediated, among other things, by two groups of enzymes. One group (proteases) "cuts" the tissue proteins and fibers, so that cells can pass through; Whereas the other group (lysyl oxidases) "pairs" and packages the texture proteins and stabilizes them. This process - the shearing of the tissue and its fusion - occurs, for example, during the healing of the skin and any other tissue after an injury.
When the functions of the body are normal, the cutting enzymes are removed from the system at the end of their action. But in a disease state, sometimes the enzymes get out of control, and then the cutting is done in an uncontrolled way. "The result is a shearing of the tissue fibers, in addition to an uncontrolled release of molecular signals from the connective tissue," says Prof. Sagi, "and all of this leads to an uncontrolled migration of cells, including pathological cells, i.e. certain cancer cells, which themselves are equipped with the same "Scissors" that allow them to make their way in order to create metastases."
the research, recently published Prof. Sagi and her group members in the scientific journal PNAS, was performed on tissue rich in collagen fibers. In the process, they showed that the cutting enzymes leave their signals in the tissue they cut, while changing the shape of the protein fibers and the biochemical composition of the cut area (through the release of molecules and proteins from the connective tissue). "Observing the 'destroyed' tissue today teaches us about the existence of a disease, even before the appearance of normal symptoms," says Prof. Sagi. This study was carried out in collaboration with the research groups ofProf. Ido Amit from the Department of Immunology at the Institute, and Prof. Hideaki Nagase from the University of Oxford.
Understanding the role of the intercellular tissue, and developing ways to protect it, may allow, in the future, the diagnosis, slowing down - and perhaps even stopping - of various types of diseases."
In another study, recently published In the scientific journal The Journal of Experimental Medicine, the scientists showed that in pathological processes, the cells of the immune system (macrophages) participate in the construction of the connective tissue. This is how the scientists discovered that the immune system mediates the construction of the collagen skeleton of the connective tissue. In experiments on mice with colon cancer, it became clear that the molecules that make up the collagen skeleton in the intercellular tissue of the tumor are secreted in an increased manner in the presence of macrophages. The "brother enzymes" also work in this situation in an increased manner. Because of this, the connective tissue is excessively thickened, and the construction of an environment that supports the tumor cells is possible. "When we interfered with a certain population of immune cells from reaching the tumor, there was a significant slowdown in the rate of its spread," says Prof. Sagi. This study was carried out together with the research groups of Prof. Chen Verol and Dr. Tamar Giger from Tel Aviv University.
In further research, Published In the scientific journal Cancer Research, the scientists succeeded in neutralizing the activity of the "fraternal enzymes" in the connective tissue, using advanced biophysical tools. In this way, the scientists were able to develop an antibody, which is able to control the uncontrolled fusion of collagen in the tissue, which may cause increased growth of the tumor cells and block the path of medicinal substances to the tumor area. In these experiments, which were carried out in mice in collaboration with the research group of Prof. Yossi Jordan From the Department of Biological Control at the Institute, the scientists were able to prevent the thickening of the connective tissue and preserve it in its normal state, which enabled a significant slowing down of the development of the tumor.
The principle of protecting and stabilizing the connective tissue as a therapeutic measure was recently illustrated in a study Published In the scientific journal Cell Host & Microbee. This study, which was carried out together with Prof. Amit's research group, showed that by inhibiting one cutting enzyme it is possible to protect the connective tissue of the lung from uncontrolled destruction, thus improving the body's functions during illness, which greatly increases the chances of survival and recovery from infectious diseases.
The principle of protection and stabilization of the connective tissue as a therapeutic measure was recently demonstrated in a study published in the scientific journal Cell Host & Microbe. This study, which was carried out with Prof. Amit's research group, showed that by inhibiting one cutting enzyme it is possible to protect the lung's connective tissue from uncontrolled destruction and thus improve the body's functions during illness, which greatly increases the chances of survival and recovery from infectious diseases.
In this case, experiments were carried out on mice suffering from influenza and pneumonia - a disease condition involving infection with a virus and a bacterium that also leads to the destruction of the connective tissue of the lung, mainly due to an out-of-control MT1-MMP cutting enzyme. In the absence of protection of the connective tissue during the viral flu illness, it is easier for the pneumonia bacteria to invade the body and settle in the destroyed tissue, reproduce there and cause a bacterial disease such as pneumonia. Therefore, when a virus or bacteria is treated, and at the same time the connective tissue is preserved - the protection of the body's systems is maximal and enables healing. "These series of studies show", concludes Prof. Sagi, "that understanding the role of the intercellular tissue, and developing ways to protect it, may allow, in the future, the diagnosis, slowing down - and perhaps even stopping - of various types of diseases."
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Collagen makes up 35-25% of all proteins in the body, and makes up about 6% of the body's weight.
