They determine the molecular mechanisms related to the regeneration of biological tissues

2024-08-06 09:15:50

A recent study provides new data and insight into how the molecular mechanisms related to the regeneration of biological tissues work.

The research focuses on tumor necrosis factor (TNF-alpha) and its TNFR receptors, substances that are of great interest to biomedicine due to their role in several diseases such as obesity related to type 2 diabetes mellitus, inflammatory bowel disease sizes and types of cancer.

The study has been led by Professor Florenci Serras, from the Department of Psychology at the University of Barcelona (UB) and the Institute of Biomedicine of said university (IBUB). Experts from the UB’s Interdisciplinary Research Center (IRBIO), the Center for Genomic Regulation (CRG) in Barcelona and the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) in Barcelona also participated in the project.

The results of the study show that tumor necrosis factor (TNF-alpha) – a protein that regulates cellular activity – has two TNFR receptors that are capable of showing completely opposite functions in response to injuries to biological tissues. -body: important, one receptor increases cell life. and regeneration, while the other is capable of promoting cell death.

The study, carried out with the Drosophila melanogaster fly as a research model, may contribute to the design of TNFR receptor agonist and antagonist agents that stimulate the regeneration of epithelial cells in patients with severe burns, or those with effected by inflammatory bowel diseases and some cancers.

Drosophila: a model to study human diseases

Communication between cells is a decisive process in the development and physiology of organisms. One of the cellular communication pathways is the secretion of substances, for example, tumor necrosis factor (TNF-alpha), which has certain functions in cells, tissues and organs.

“Essentially, the secreted tumor necrosis factor is able to recognize and bind to its receptor TNFR, which is on the surface of neighboring cells. As a result of the characteristic, the TNFR receptor is activated and regulates different processes such as cell adhesion, cell death or adaptive immunity,” explains Florenci Serras, member of the Department of Genetics, Microbiology and Statistics of the UB.

In the mammalian genome, there are nineteen TNF molecules and twenty-nine TNFR receptors, which shows the great complexity of their research in the case of humans. However, some organisms such as the fly D. melanogaster have a tumor necrosis factor (called Eiger, Egr) and two unique TNFRs, which are receptors Grindelwald (Grnd) and Wengen (Wgn).

“Thanks to this simplicity, and adding the many genetic tools of Drosophila, we have been able to use this model organism to study the structure and function of TNF-alpha/TNFR,” said the researcher.

Some receivers have opposite functions

Although TNF-alpha and TNFR receptors are linked to acute and chronic diseases, “we still do not know well how these components control cellular processes as opposed to cell death or cell survival, and even cell proliferation,” Serras emphasized. .

The new work, which will be included in the doctoral thesis that the doctoral student José Esteban-Collado will defend, provides evidence that supports the different and opposite functions of TNFR Grnd and Wgn. “In one way, the Grnd receptor promotes cell death (apoptosis) to eliminate damaged cells through the TRAF2-dTAK1-JNK pathway in a TNF-alpha Egr-dependent manner,” Serras said. “On the other hand, the Wgn receptor promotes the survival and regeneration of cells to maintain healthy tissues and in good condition, through the TRAF1-Ask1-p38 pathway and without the need for TNF-alpha Egr,” he said. supplement.

“That is, the first receptor needs a ligand to bind to the receptor, while the second can be activated without interacting with the ligand. Therefore, each TNFR promotes its own signal to achieve different functions,” Florenci Serras explained. “Therefore, communication mechanisms of TNFRs must ensure a balance between the functions of the different TNFRs, the molecular signals they set in motion, and their dependence-or not-on the ligand (TNF-alpha),” he pointed out.

Damaged cells emit molecular signals in healthy ones

When a cell dies or is damaged, it communicates with healthy cells to replace the non-functioning cell with a new one and thus start the regeneration of the affected tissue. The study describes how dead cells release reactive oxygen species (ROS), which are taken up by active cells in their environment to stimulate the regeneration process of the affected tissue.

“In a pathological condition or tissue damage, both receptors show different responses. First, the affected skin produces TNF-alpha Egr, which binds to Grnd on the skin. This is intrinsic and promotes suicide due to cell death (apoptosis). At the same time, these cells produce ROS, which spread and reach healthy cells as an alarm signal that indicates tissue damage,” explained Serras. “ROS signaling activates Wgn in healthy cells directly, without the need for Egr, and as a result activates a signaling pathway that promotes tissue survival, protection and regeneration,” Serras explained.

The art of entertainment is dead cell. (Credit: Amazing Things/NCYT)

The results of the new study support a model in which ROS from damaged tissues are capable of activating Wgn signaling in healthy cells in the region to promote their regeneration.

Using an intelligent binary system that allows a gene to be manipulated in specific areas of the body, the study authors have also determined the important role for TNFR Wgn-but not Grnd-in the activation of p38 kinase. “In healthy cells, this p38 will be responsible for the activation of all the genetic machinery in order to repair the tissue,” concludes Florenci Serras.

The study is titled “Reactive oxygen species activates the Drosophila TNF receptor Wengen for inflammatory regeneration.” And it has been published in the academic journal The EMBO Journal. The significance of the study is due to be highlighted in the News & Views section of the said magazine. (Source: University of Barcelona)