The phenomenon of “self-eating” cells in the pathogenesis of endometriosis
The project titled “The influence of autophagy on the expression of chromogranin A in endometrial cells” is carried out under the supervision of habilitated doctor Izabela Janiuk, and professor Jacek Malejczyk from the Department and Section of Histology and Embryology of the Medical University of Warsaw. These studies aim to answer the question whether inducing the “self-eating” process in endometrial cells results in the expression of selected proteins that may participate in the pathogenesis of endometriosis.
What is endometriosis?
The world of medicine is full of complexities and unknowns. One of them is endometriosis – a disease that constitutes a troublesome problem for patients and a considerable diagnostic challenge for doctors. Endometriosis is the presence of lesions resembling the uterine mucosa in other tissues and organs. Endometriosis manifests itself with painful periods and constant or recurrent pain in the pelvic area or abdominal cavity, which can lead to anxiety and depression. It is a disease occurring in approximately 10% of women of reproductive age, including approximately 20-50% of patients with infertility, which means that endometriosis is considered one of the important causes of this common problem. Taking into account current statistics, every sixth woman of reproductive age is affected by fertility dysfunction! Treatment for endometriosis includes hormone therapy, and ultimately surgery, and is not fully effective.
Endometriosis diagnosis
Unfortunately, we still do not have good tools for minimally invasive diagnosis of endometriosis. The final diagnosis is made using laparoscopic methods and ten years, on average, pass from the onset of symptoms to diagnosis. The pathogenesis of this disease is still not fully understood but the suspects are metaplasia (the appearance of changed cells in the tissue), inflammatory processes and malfunctioning of the immune and hormonal systems and angiogenesis. Genetic, epigenetic and environmental factors probably also play a role. However, it is still unknown what facilitates the implantation and survival of endometrial cells (originating from the uterine mucosa) in other locations within the pelvis and what causes the associated inflammatory reactions.
About the project and research on endometriosis
“Thanks to habilitated doctor Izabela Janiuk, and professor Jacek Malejczyk from the Department and Section of Histology and Embryology of the Medical University of Warsaw, I joined the team conducting research on this disease. The aim of the project is to decipher the complex processes underlying endometriosis.
Our interests include intracellular processes that may participate in the development of lesions in the course of endometriosis. According to information appearing in the world literature, we hypothesize that these lesions may be related to the autophagy pathway. But what exactly connects this cellular pathway with the development of endometriosis that is not only an individual but also a social problem? We hope that this question will be answered soon.”
Autophagy – the “self-eating” of cells
Autophagy is a catabolic process that occurs physiologically in all body cells in response to nutrient deficiency, hypoxia (oxygen deficiency), oxidative stress (caused by the negative impact of free radicals) or organelle damage. There are several types of autophagy: macroautophagy, microautophagy and autophagy mediated by chaperones (accessory proteins). Macroautophagy is the best known type. When a cell is exposed to unfavorable conditions, it covers some of its cytoplasmic structures that are redundant or damaged with a membrane originating from the endoplasmic reticulum. The separating membrane then closes and a vesicle is formed that fuses with the lysosome. Finally, lysosomal enzymes digest the isolated cellular elements. Autophagy enables cells to survive by degrading and recycling these structures. This is why self-eating may be a factor facilitating the survival of endometrial cells outside their natural location. Under certain conditions, autophagy also serves as one of the types of apoptosis. Autophagy disorders occur in neurodegenerative and cancer diseases, among others.
Determining the mechanism linking autophagy and endometriosis
To determine what mechanism connects autophagy with the development of endometriosis, we will check what factors are expressed in response to the induction of this process in endometrial cell lines. One of the molecules tested is chromogranin A. It is a protein prohormone produced in nerve and neuroendocrine cells. The main source of this substance in the human body are the adrenal medulla and the pancreatic islets where it participates in the regulation of insulin secretion into the bloodstream. Chromogranin A is also the most important representative of the family of secretory proteins called “granins”, of which it is the precursor. This group includes numerous regulatory peptides, such as vasostatin, pancreastatin and catestatin. Mediated by these peptides, chromogranin A modulates the function of the immune system, the cardiovascular system and angiogenesis, among others.
An increase in the concentration of chromogranin A has been found in the bloodstream of patients with certain cancer and autoimmune diseases, for example multiple sclerosis, as well as in patients with hypertension, heart failure and kidney failure. Chromogranin A is also one of the autoantigens in type 1 diabetes. This protein is used as a marker for neuroendocrine tumors, i.e. tumors originating from hormone-secreting cells. Such diseases include, for example, pheochromocytomata of the adrenal glands. Due to the similarity of the pathogenesis of endometriosis and the diseases mentioned above (autoimmunity and metaplasia), it is probable that chromogranin A also plays an important role in this condition. Moreover, research recently conducted at the Department and Section of Histology and Embryology has shown that this peptide may influence the local production of cytokines and inflammatory reactions in the pelvis minor.
The role of autophagy, chromogranin A and the mechanisms of chromogranin expression in endometriosis remain unknown and have not been the subject of consideration until now. Conducting planned experiments may reveal previously unknown mechanisms of endometriosis development. This knowledge may contribute not only to a better understanding of the pathogenesis of the disease, but also suggest new diagnostic and therapeutic targets.
Maja Owe-Larsson is a fourth-year medical student of the Medical University of Warsaw, third place winner in the Polish Physiological Society’s “Great Synapse” competition (2022), leader of the project “Determining the usefulness of CgA expression in non-invasive diagnosis of endometriosis” (financed by the Ministry of Science and Higher Education in the “Student science clubs create innovations” competition) and winner of the “Talents of Tomorrow” grant program (under which it is possible to implement the described project “The influence of autophagy on the expression of chromogranin A in endometrial cells”).