Ecological aspects of molecular mechanisms of epigenetic rearrangement of humoral systems of the renal function regulation

Sergey Dolomatov, Tatiana Sataieva, Walery Zukow, Yulia Kondakova, Edie Ramazanova



Epigenetic transformation of chromatin is able to be induced by environmental factors and changes in the parameters of the state of metabolic processes in the body. Among them, the most common known factors are hypoxia (ischemia of the organ), hyperglycemia, heavy metals, endocrinopathies, infectious diseases.

The results of the review conclude that epigenetic mechanisms pay the very important contribution to the restructuring of humoral systems of renal regulation during renal failure sufficiently contributing to a progressive reduction of nephrons and directly preconditioning the unfavorable progress of the disease. In considering this potential etiologic factor, one must take into account several common triggers changing the epigenetic transformation of intrarenal synthesis and metabolism of physiologically active substances. Primary it is the formation of atypical foci of their products, which is most evident in the processes of restructuring of the RAS and nitric oxide systems. Secondary the renal coordinating humoral factors increasingly lose the control of regulation of homeostasis and switch on the pathophysiological way of progressive renal failure. Next are the epigenetic changes of proteins genes that perform key functions in the synthesis and metabolism of humoral factors in the regulation of renal functions. Uncontrolled synthesis of these peptides leads to a triggered enhancement of the process, again, involving epigenetic chromatin rearrangement.

The indicated regularity can be traced to unrestricted activation of RAAS and the renal system of TGF-beta. Other contributing factors occur as a result of unrestricted activation of RAAS and the TGF-beta system. On this background, there is a steady decline in the regulatory capabilities of the opposition control vector represented by the nitrogen oxide system, primarily by the constitutive isoforms eNOS and nNOS. The research of epigenetic processes during various nephropathies does not only enlightens theoretical basis for the pathogenesis of renal failure but also opens promising approaches for the development of new pharmacological corrects of renal function.


kidneys; renal failure; epigenetics; renin-angiotensin-aldosterone system; transforming growth factor beta; nitric oxide

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