FIBROSIS: POLYETIOLOGIC COMPLICATION WITH COMMON DENOMINATOR
Authors: Zabolotnyi Dmitry , Dieieva Yuliia , Gurzhenko Yurii , Zabolotna Diana , Gordiienko Iuliia , Tymchenko Marina , Voroshylova Natalia , Pakrishen Svіtlana , Verevka Serhij 
Published: November 2021

State of the problem. The growth of fibrous connective tissue is a common complication of various pathological processes, which significantly complicates recovery and is one of the leading causes of death. Despite many years of research, the process of fibrosis development remains insufficiently studied and contains a large number of “white spots”. Fibrosis is characterized by unpredictability, propensity to grow and low level of the replacement by normal connective tissue. The structure of fibrous tissue, its differences from normal and the reasons for the formation of these differences deserve no less attention. The formation of fibrous tissue is preceded by the process of endogenous intoxication – the formation and accumulation of various abnormal metabolites. Among the latter, the leading place belongs to proteins and peptides, whose structure is disrupted and destabilized. It is known that destabilized proteins are prone to aggregation. This process, contrary to popular belief, is not chaotic, but is subject to certain laws and is aimed at minimizing of free energy. With regard of the latter circumstance a definite favorite is the formation of β-structured fibrils, which occupy almost the lowest energy level among protein conformational states. Such fibrils are characterized by insolubility, resistance to proteolysis, immunogenicity and the ability to autochthonous growth due to sorption and conformational rearrangement of soluble proteins. A classic example of such aggregation is amyloid formation, but there are good reasons to assume similar processes in the formation of other pathological tissues.
The aim of the work was to verify experimentally the presence of β-structured protein aggregates in fibrous tissues, which differ in etiology.
The methodical part included the selection of surgical material, its fixation in 10 % formaldehyde solution, preparation of Congo-stained red histological specimens and microscopic examination in light, polarization and fluorescence modes.
Results. The presence of β-structured protein aggregates in fibrous tissues formed due to local chronic inflammation, viral infection and side effects of drugs has been proven experimentally. The identified phenomenon allows us to approach the understanding of the mechanisms of fibrosis development and to postulate a key role of regular aggregation of destabilized proteins.
Conclusions. The obtained data testifies to a general and integral participation of β-structured protein aggregates in the formation of fibrous tissues of different etiologies. The presence of these deposits in fibrous tissues formed due to local chronic inflammation, viral infection and side effects of the cytostatic doxorubicin has been shown. The leading role of violation of protein homeostasis and local accumulation of structurally damaged proteins as a prerequisite for autochthonous aggregation process is discussed. The expediency of fluorescence microscopy has been shown, which significantly expands the possibilities of detecting with the help of the Congo red of nanosized β-structured protein aggregates, which are invisible due to Abbe's limitations in light and polarization microscopy.
Key words: fibrosis, keloidosis, Peyronie’s disease, Covid-19, cytostatics, nanoparticles.