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Depiction of this model of lymphoblastic leukaemia. Normal B-cell development proceeds from haematopoietic stem cells (HSC) through multiple stages to ultimately become mature B cells. A small subset of pro-B cells express renin and are termed BRenin-cells. In this model, activation of the renin promoter in BRenin-cells results in cre recombinase expression and subsequently RBP-J deletion. These cells fail to differentiate along the normal B-cell pathway, undergo epigenetic activation and enrichment of a precursor B-cell gene programme. Mutant cells additionally experience cell cycle progression and cell proliferation ultimately resulting in expansion of a lymphoblast population and the development of precursor B cell leukaemia.
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The cell of origin and triggering events for leukaemia are mostly unknown. Here we show that the bone marrow contains a progenitor that expresses renin throughout development and possesses a B-lymphocyte pedigree. This cell requires RBP-J to differentiate. Deletion of RBP-J in these renin-expressing progenitors enriches the precursor B-cell gene pr...
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Context 1
... the mutant, the levels of Igll1, Enpep, Rag1, Vpreb1 and Vpreb3 as measured by qRT-PCR were even more elevated (1,410-, 73-, 59-, 1,131-and 13-fold, respectively) than in the microarray array data, suggesting that the microarray detection had reached saturation for these transcripts. Further, we performed qRT-PCR from a pure population of cultured GFP þ leukaemic cells and found a similar pattern of upregulation of genes marking early B-cell development including VpreB1, Igll1 and VpreB3 ( Supplementary Fig. 8). ...
Context 2
... summary, we identified novel bone marrow progenitors, which express renin and become the source of lymphoblastic leukaemia when RBP-J is missing (Fig. 8). The possibility that within the B-cell population there are subsets of progenitors with differential transformative capacity has significant implications for understanding the origin of leukaemia. The discovery of these progenitors, the reproducibility of this highly penetrant mouse model of leukaemia, and the generation of a new GFP ...
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Background
The purpose of this study was to describe the natural history of severe congenital neutropenia (SCN) in 14 patients with G6PC3 mutations and enrolled in the French SCN registry.Methods
Among 605 patients included in the French SCN registry, we identified 8 pedigrees that included 14 patients with autosomal recessive G6PC3 mutations.Resul...
Citations
... To test this hypothesis, we inactivated Tcf21 in renin expressing cells by breeding Tcf21 f/f mice with Ren1dCre + mice (which express cre recombinase driven by the renin locus) to create the Ren1 dCre/+ ;Tcf21 f/f (Tcf21 renin cKO) mouse. The Ren1 dCre+ model, in which Crerecombination facilitates conversion of mTomato to GFP expression, has been previously characterized for tracing of the JG cell lineage (19)(20)(21). Following immunostaining with the pan-endothelial marker PECAM (CD31) and 3D image analysis of cleared E16.5 kidneys, we observed no difference in the vascular morphology of the Tcf21 renin cKO compared with controls ( Fig.3 I, Suppl. ...
Renin is a crucial enzyme involved in the regulation of blood pressure and electrolyte balance. It has been shown that renin expressing cells arise from the Foxd1+ stromal progenitors, however the factors involved in guiding Foxd1+ cells towards the renin-secreting cell fate remain poorly understood. Tcf21, also known as Pod1 or Capsulin, is a bHLH transcription factor that is expressed in the metanephric mesenchyme and plays a crucial role in kidney development. We have previously shown that deletion of Tcf21 in Foxd1+ cells (Foxd1Cre/+;Tcf21f/f) results in paucity of vascular mural cells and in disorganized renal arterial tree with fewer, shorter, and thinner arterioles. Here, we sought to examine the relationship between Tcf21 and renin cells during kidney development and test whether Tcf21 is implicated in the regulation of juxtaglomerular cell differentiation.
Immunostaining for renin demonstrated that kidneys of Foxd1Cre/+;Tcf21f/f have fewer renin-positive spots at E16.5 and E18.5 compared with controls. In-situ hybridization for renin mRNA showed reduced expression in Foxd1Cre/+;Tcf21f/f kidneys at E14.5, E16.5, and E18.5. Together, these data suggest that stromal expression of Tcf21 is required for the emergence of renin cells. To dissect the role of Tcf21 in juxtaglomerular (JG) cells, we deleted Tcf21 upon renin promoter activation (Ren1dCre/+;Tcf21f/f). Interestingly, the Ren1dCre/+;Tcf21f/f kidney showed normal arterial tree at E16.5 identical to controls. Furthermore, inactivation of Tcf21 upon renin expression did not alter kidney morphology in two- and four-month-old mice. Finally, expression renin mRNA was similar between Ren1dCre/+;Tcf21f/f and controls at 2 months.
Taken together, these findings suggest that Tcf21 expression in Foxd1+ cells is essential for specifying the fate of these cells into juxtaglomerular cells. However, once renin cell identity is assumed, Tcf21 is dispensable. Uncovering the regulation of Foxd1+ cells and their derivatives, including the JG cell lineage, is crucial for understanding the mechanisms underlying renal vasculature formation.
... Presumably, the tumors in these mutant mice are due to cre-recombinase activity outside of the kidney, specifically within B-1 progenitors of the hematopoietic system or within renin-expressing cells in the yolk sac which has been recently reported (36,37). Further work will be needed to determine the origin and identity of these tumors. ...
Polycystic kidney disease (PKD) is an inherited disorder that results in large kidneys, numerous fluid-filled cysts, and ultimately end stage kidney disease. PKD is either autosomal dominant caused by mutations in PKD1 or PKD2 genes or autosomal recessive caused by mutations in the PKHD1 or DZIP1L genes. While the genetic basis of PKD is known, the downstream molecular mechanisms and signaling pathways which lead to deregulation of proliferation, apoptosis, and differentiation are not completely understood. The Notch pathway plays critical roles during kidney development including directing differentiation of various progenitor cells, and aberrant Notch signaling results in gross alternations in cell fate. In this study, we generated and studied transgenic mice which have overexpression of an intracellular fragment of mouse Notch1 (“NotchIC”) in renin-expressing cells. Mice with overexpression of NotchIC in renin-expressing cells developed numerous fluid-filled cysts, enlarged kidneys, anemia, renal insufficiency, and early death. Cysts developed in both glomeruli and proximal tubules, had increased proliferation marks, and had increased levels of Myc. This work implicates the Notch signaling pathway as a central player in PKD pathogenesis and suggests the Notch-Myc axis may be an important target for therapeutic intervention.
... www.nature.com/scientificreports/ the proportion of renin cells in the peritoneal cavity is maintained throughout adult life, their proportion in the bone marrow and spleen diminishes with age ( Fig. 1g). Renin lineage (GFP + ) cells from the bone marrow, spleen, and peripheral blood are B-2 B lymphocytes (B220 + CD19 + CD23 +/− CD11b − ) 4 . However, renin progenitors in the peritoneal cavity are B-1 B cells (B220 dim CD23 − CD11b + CD5 +/− ) (Fig. 1h,i). ...
... Whereas most of them stop producing renin, the kidney juxtaglomerular cells and the B-1 lymphocytes retain the ability to synthesize renin in adult life 1 . Interestingly, these two cell types share some core transcriptional regulators 4 . We have previously shown that deletion of RBP-J in the mouse kidney alters the fate of renin cells. ...
The hormone renin plays a crucial role in the regulation of blood pressure and fluid-electrolyte homeostasis. Normally, renin is synthesized by juxtaglomerular (JG) cells, a specialized group of myoepithelial cells located near the entrance to the kidney glomeruli. In response to low blood pressure and/or a decrease in extracellular fluid volume (as it occurs during dehydration, hypotension, or septic shock) JG cells respond by releasing renin to the circulation to reestablish homeostasis. Interestingly, renin-expressing cells also exist outside of the kidney, where their function has remained a mystery. We discovered a unique type of renin-expressing B-1 lymphocyte that may have unrecognized roles in defending the organism against infections. These cells synthesize renin, entrap and phagocyte bacteria and control bacterial growth. The ability of renin-bearing lymphocytes to control infections—which is enhanced by the presence of renin—adds a novel, previously unsuspected dimension to the defense role of renin-expressing cells, linking the endocrine control of circulatory homeostasis with the immune control of infections to ensure survival.
... Lineage tracing studies also demonstrated renin expression outside the kidney including hematopoietic tissues, testis, adrenal glands, Müller cells, central nervous system, and skin [3,19]. The vast heterogeneity in renin-expressing cells transcending organs and embryonic layers raises fascinating questions. ...
... As mentioned previously, renin-producing hematopoietic cells may be involved in immune responses. These renin-expressing, hematopoietic progenitors first appear in the primitive yolk sac followed by their occurrence in the spleen, liver, bone marrow, and peripheral blood [19,21]. The cells are immature progenitor B lymphocytes. ...
Hypotension and changes in fluid–electrolyte balance pose immediate threats to survival. Juxtaglomerular cells respond to such threats by increasing the synthesis and secretion of renin. In addition, smooth muscle cells (SMCs) along the renal arterioles transform into renin cells until homeostasis has been regained. However, chronic unrelenting stimulation of renin cells leads to severe kidney damage. Here, we discuss the origin, distribution, function, and plasticity of renin cells within the kidney and immune compartments and the consequences of distorting the renin program. Understanding how chronic stimulation of these cells in the context of hypertension may lead to vascular pathology will serve as a foundation for targeted molecular therapies.
... Angiotensin peptides and steroid hormones were symbolized in gray. Lymphoid cells cannot differentiate throughout the normal B-cell pathway (40). Therefore, the leader B-cell gene undergoes epigenetic initiation and enrichment of a precursor B-cell gene programme. ...
... As a result, cell cycle progression and cell proliferation are observed in mutant cells. This leads to the enlargement of a lymphoblast population and the development of leading B cell leukemia (5,19,23,38,40,41). HSPC, Hematopoietic stem/progenitor cells; ACE, Angiotensin converting enzyme; CML, Chronic myeloid leukemia; Ang, Angiotensinogen; CFU-GM/E, Colonyforming units-Granulocyte-Macrophage/erythroid; JAS/STAT, Janus kinase/Signal transduction and transcription; BC, Blood cell; Ang, Angiotensin; Preg, Pregnanolone; Prog, Progesterone; DOC, deoxycortisol; 17-OHP, 17-OH Progesterone; ACE, angiotensin I converting enzyme; ACE2, angiotensin I converting enzyme type 2; AGTR1, angiotensin II type 1 receptor; AGTR2, angiotensin II type 2 receptor; AKRIC4, aldo-ketoreductase family 1 member C4; AKRID1, aldo-ketoreductase family 1 member D1; ANPEP, alanyl-aminopeptidase; ATP6AP2, prorenin/renin receptor; CMA1, chymase 1; CPA3, carboxypeptidase A3; CTSA, cathepsin A; CTSD, cathepsin D; CTSG, cathepsin G; CYP11A1, cytochrome P450 family 11 subfamily A polypeptide 1; CYP11B1, cortisolsynthase; CYP11B2, aldosteronesynthase; CYP17A1, cytochrome P450 family 17 subfamily A polypeptide 1; CYP21A2, cytochrome P450 enzyme family 21 subfamily A polypeptide 2; DPP3, dipeptidyl-peptidase 3; ENPEP, glutamylaminopeptidase (aminopeptidase A); GR, glucocorticoidreceptor; HSD11B1, hydroxysteroid (11-beta) dehydrogenase 1; HSD11B2, hydroxysteroid (11-beta) dehydrogenase 2; IGF2R, insulin-like growth factor 2 receptor; KLK1, tissuekallikrein; LNPEP, leucyl/cystinylaminopeptidase; MAS1, MAS1 proto-oncogene; MME, membranemetallo-endopeptidase; MR, mineralocorticoidreceptor; NLN, neurolysin (metallopeptidase M3 family); PREP, prolylendopeptidase; REN, renin; RNPEP, arginylaminopeptidase (aminopeptidase B); THOP1, thimetoligopeptidase 1. Images of IGF2R36, ATP6AP237, MR38, GR39, G-protein coupled receptors (AGTR1, AGTR2, GPER, and MAS1) 40 and LNPEP41 (19). ...
Circulating renin-angiotensin system (RAS) and local paracrin-autocrin-intracrin tissue-based RAS participate in numerous pathobiological events. Pro-inflammatory, pro-fibrotic, and pro-thrombotic consequences associated with local RAS activation have been detected at cellular and molecular level. Regenerative progenitor cell therapy in response to RAS modulating pharmacotherapy has emerged as an adjunct in the context of endothelial cell injury and regeneration to improve regeneration of the vascular endothelium. Local hematopoietic bone marrow (BM) RAS symbolizes the place of cross-interaction between vascular biology and cellular events from embryogenesis to definitive hematopoiesis underlying vascular atherosclerosis. The BM microenvironment also contains Mas receptors, which control the proliferative role of Ang 1-7 on hematopoietic stem cells. Ang 1-7 is produced from Ang-II or Ang-I with the help of ACE2. Various tissues and organs also have an effect on the RAS system. The leukocytes contain and synthesize immunoreactive angiotensinogen species capable of producing angiotensin in the basal state or after incubation with renin. The significance of RAS employment in atherosclerosis and hypertension was indicated by novel bidirectional Central Nervous System (CNS) RAS–BM RAS communications. Myeloid cells generated within the context of hematopoietic BM RAS are considered as the initiators and decision shapers in atherosclerosis. Macrophages in the atherosclerotic lesions contain angiotensin peptides by which RAS blockers inhibit monocyte activation and adherence. Furthermore, vascular biology in relation to inflammation and neoplasia is also affected by local tissue RAS. The purpose of this article is to outline interactions of circulating and local angiotensin systems, especially local bone marrow RAS, in the vascular pathobiological microenvironment of CNS.
... Plasma renin concentration was determined using ELISA following the manufacturer's instructions (RayBiotech) as we previously described. 29 ...
Aim
Renin cells are essential for regulation of blood pressure and fluid‐electrolyte homeostasis. During homeostatic threat, the number of renin cells in the kidney increases, a process termed recruitment. It has been proposed that recruitment occurs by proliferation, yet no systematic studies have been performed. We sought to determine the extent to which proliferation contributes to the recruitment process.
Methods
Mice were subjected to recruitment before analysing the renin cells’ cell cycle. For acute threats, we subjected SV129 and C57Bl6 mice to a low sodium diet plus captopril. Tissue sections from treated mice were co‐stained for proliferation markers (Ki67, PCNA, pH3, Brdu) and renin. Chronic recruitment was studied in deletion models of Aldosterone‐synthase and Angiotensinogen through co‐immunostaining and counting mitotic figures in Periodic‐Acid‐Schiff stained sections. Finally, RNA‐seq of renin cells isolated from recruited mice was performed to study mitotic signature.
Results
Mice subjected to low salt and captopril displayed increases in renin cell number (312 +/‐40 in controls to 692 +/‐85 in recruited animals, p<.0001), 10‐fold increases in renin mRNA, and 4‐fold increases in circulating renin. Co‐staining these kidney sections for proliferation markers revealed negligible proliferation of renin cells (<2%), indistinguishable from control animals. Similarly, chronic models of recruitment – Aldosterone‐synthase‐KO and Angiotensinogen‐KO – had negligible proliferation. Additionally, the transcriptome of recruited renin cells revealed overall downregulation of mitotic pathways when compared to proliferative cell lines.
Conclusion
Acute and chronic physiological threats to homeostasis produced a distinct increase in renin‐synthesizing cells, but we found no evidence to suggest involvement of proliferation.
... In this model, nonrecombined cells express mTomato, and upon Cre-recombination, renin-expressing cells and their descendants become GFP (green fluorescent protein)+. 12 Mutant mice were monitored for signs and symptoms of disease. When moribund, mutants and littermate controls were anaesthetized with tribromoethanol (300 mg/kg); organs were removed, preserved for RNA extraction or fixed for immunohistochemistry. Forty mutant mice of both sexes between 2 and 6 months of age are included in this study with equal numbers of age-matched controls. ...
... 20 Plasma renin concentration was determined by ELISA as described. 12,21 ...
... 14 The expression of AKR1B7 was also reduced in the cKO kidneys indicating that its expression was similarly affected by Itgb1 deletion or that renin cells were transformed into other cell type(s) or that they had simply died. To address these questions, we traced the fate of GFP+ cells from the renin lineage, 12 Whereas in the control kidneys GFP+ arteriolar renin cells were distributed in the classic JGA, along the walls of the afferent arterioles, and in the SMCs of intrarenal arteries, in the mutants kidneys, cells from the renin lineage were not present along the arterioles or in the JGAs. The reduction in the number of renin cells was likely secondary to the loss of integrin-mediated survival signals. ...
Juxtaglomerular cells are crucial for blood pressure and fluid-electrolyte homeostasis. The factors that maintain the life of renin cells are unknown. In vivo, renin cells receive constant cell-to-cell, mechanical, and neurohumoral stimulation that maintain their identity and function. Whether the presence of this niche is crucial for the vitality of the juxtaglomerular cells is unknown. Integrins are the largest family of cell adhesion molecules that mediate cell-to-cell and cell-to-matrix interactions. Of those, β1-integrin is the most abundant in juxtaglomerular cells. However, its role in renin cell identity and function has not been ascertained. To test the hypothesis that cell-matrix interactions are fundamental not only to maintain the identity and function of juxtaglomerular cells but also to keep them alive, we deleted β1-integrin in vivo in cells of the renin lineage. In mutant mice, renin cells died by apoptosis, resulting in decreased circulating renin, hypotension, severe renal-vascular abnormalities, and renal failure. Results indicate that cell-to-cell and cell-to-matrix interactions via β1-integrin is essential for juxtaglomerular cells survival, suggesting that the juxtaglomerular niche is crucial not only for the tight regulation of renin release but also for juxtaglomerular cell survival-a sine qua non condition to maintain homeostasis.
... While studying the effects of RBP-J deletion in the kidney, we found that as the mice aged, they developed signs of a highly penetrant and devastating form of pre-B-cell leukemia. 60 Therefore, we performed an extensive series of experiments to characterize not only the disease but also to identify its cell of origin. We found that cells from the bone marrow, spleen, Peyer patches, and lymph nodes normally contain a group of primitive lymphocytes that synthesize and release renin. ...
... These renin cells with a lymphocyte pedigree display some developmental, biochemical, and transcriptional similarities with the more distant kidney juxtaglomerular cell. 60 Similar to juxtaglomerular cells, renin-bearing lymphocytes in the bone marrow and spleen decrease in number as development progresses. Remarkably, at all ages examined, these cells are proportionally 10 times more abundant than juxtaglomerular cells. ...
... B renin cells and juxtaglomerular cells also have in common the expression of some transcription factors such as EBF1, a well-known regulator of lymphocyte development, Ikaros, EPAS1 (HIF2α), Notch receptors, and RBP-J. 60 This suggests a conservation of a portion of the transcriptional machinery and a possible lineage relationship between hematopoietic and kidney renin cells. Both cell types require RBP-J to differentiate properly. ...
A lthough renin cells are crucial for blood pressure homeo-stasis, little is known about their nature. We now know that renin cells are precursors that appear early and in multiple tissues during embryonic development. They participate in morphogenetic events, vascular development and injury, tissue repair, and regeneration. When confronted to a homeostatic threat, renin cell descendants have the capability to switch the renin gene on or off. This poorly understood switch or molecular memory enables the organism to maintain constancy of the internal milieu and tissue perfusion. Here, we discuss briefly the major events that govern the acquisition and maintenance of renin cell identity and how manipulations that alter the fate of renin cells can lead to serious disease. We also advance the concept that renin cells are at the center of an ancestral system of defense linking the endocrine, the immune, and the repair responses of the organism. Renin-Angiotensin System The renin-angiotensin system (RAS) is crucial in the regulation of blood pressure and fluid-electrolyte homeostasis. 1,2 In the traditional view of the RAS, renin is released by the kidney juxtaglomerular cells, and on reaching the circulation, it acts on its only known substrate, angiotensinogen, produced mainly in the liver to yield angiotensin I (Ang I), a decapep-tide and Des-Ang I-angiotensinogen, a large molecule of unclear function. Thereafter, Ang I is hydrolyzed by angio-tensin-converting enzyme to yield the octapeptide Ang II, a fast acting and powerful vasoconstrictor that regulates peripheral vascular resistance, renal hemodynamics, and sodium reabsorption via several mechanisms, including the stimulation of aldosterone secretion by the adrenal glands. Most of the known cardiovascular and renal actions of the RAS are achieved by the actions of Ang II on its receptors, mainly AT1 receptors. It should be noted that for the system to operate properly, it needs to respond accurately and rapidly to changes in the composition and volume of the extracel-lular fluid and to variations in systemic blood pressure. The key regulated event in this enzymatic cascade is the tightly controlled, minute-to-minute regulation of renin release by the juxtaglomerular cells. This is possible because juxtaglo-merular cells are sensors strategically located in the juxtaglo-merular apparatus (JGA), where they receive and interpret signals that convey the composition and volume of the extra-cellular fluid and the level of perfusion pressure. The JGA is composed of the afferent and efferent arterioles, the macula densa, and the extraglomerular mesangium or polkissen. 1,3,4 In the adult unstressed mammalian kidney, juxtaglomerular cells are located in the afferent arteriole at the entrance to the glomerulus, where they make contact with macula densa cells, extraglomerular mesangial cells, and other renin and smooth muscle cells along the arteriole. 3,4 Juxtaglomerular cells have a myoepithelioid appearance; they are densely innervated by sympathetic terminals arising from the renal nerve; and they contain granules from where renin is stored and released in response to a diverse number of stimuli emanating from nearby cells, sympathetic terminal, and from the circulation. 5 Three major mechanisms control renin release by juxtaglomerular cells: (1) the renal baroreceptor mechanism, whereby renin release is elicited by a decrease in renal perfu-sion pressure as it occurs during hypotension, shock, hemorrhage , or cardiac failure. The nature of the renal baroreceptor has not been determined since its original 1959 description by Tobian et al, 6 (2) the macula densa mechanism, whereby renin release is stimulated by a decrease in sodium chloride in the distal tubule as it occurs during sodium depletion, and (3) the β-receptor-mediated mechanism, whereby stimulation of β-receptors elicited by sympathetic terminals or via circulating catecholamines such as during hypoxia results in increased renin release. Interestingly, the renal baroreceptor mechanism continues to function in the absence of the other 2 mechanisms: in the denervated, nonfiltering kidney, the barorecep-tor mechanism continues to operate suggesting that the renal baroreceptor mechanism is independent from the influence of the macula densa or the β-receptor. 2 Under normal circumstances , however, these mechanisms operate together to finely regulate renin output. For instance, the β-receptor mechanism, the baroreceptor mechanism, and the macula densa mechanism are all activated during hemorrhage, a situation where there is decreased perfusion pressure, decreased delivery of sodium chloride to the macula densa, and stimulation of the sympathetic system. It should be noted that Ang II exerts a negative feedback on renin release, a typical case where the byproduct of an enzymatic reaction controls its own production , in this case governed by the underlying physiological status of the animal. When angiotensin production and its actions are limited, such as when animals are exposed to angiotensin-converting enzyme inhibitors or AT1 receptor blockers, renin synthesis and release is increased. This is accomplished in great part by an increase in the number of cells that synthesize and release renin as described below. 7-9
... Авторы цитируемого обзора подчеркивают, что экспрессия ренина была обнаружена в клетках острого миелоидного лейкоза, в клетках хронического миелоидного лейкоза и острого лимфолейкоза. Высказывается мнение о том, что стволовые клетки костного мозга, которые экспрессируют ренин являться источником лимфобластного лейкоза (Belyea B.C. et al., 2014). По данным литературы, экспрессия гена ренина в процессе нормального и малигнизированного емопоэза может регулироваться эпигенетическими механизмами (Belyea B.C. t al., 2014; Haznedaroglu I.C., Malkan U.Y., 2016). ...
Radom, 2019 2 Dolomatov S.I., Zukow W. Эпигенетика почек = Kidneys epigenetics. RSW. Radom, 144 p. ISBN 9780359774524. DOI http://dx.doi.org/10.5281/zenodo.3270699 PBN Poland https://pbn.nauka.gov.pl/sedno-webapp/works/917606 Reviewers: dr hab. R. Muszkieta, prof. nadzw. (Poland) dr hab. M. Napierała, prof. nadzw (Poland) АННОТАЦИЯ В книге представлены сведения о роли эпигенетических механизмов в системе контроля функции почек в норме и при патологии. Результаты анализа роли эпигенетического контроля экспрессии генов транспортных и регуляторных белков почки в норме указывают, во-первых, на высокую пластичность процессов изменения экспрессии генов. Во-вторых, иллюстрируют их способность адекватно реагировать на изменения параметров гомеостатических функций почек, что, в свою очередь, позволяет рассматривать данные процессы в качестве еще одного звена управления деятельностью органа наряду с нейро-эндокринными и внутриорганными уровнями гуморального контроля водно-солевого баланса организма. Приведены факты, подчеркивающие вовлеченность гуморальных факторов системного действия и внутрипочечных систем гуморального контроля в процессы эпигенетической перестройки экспрессии генов ренальной паренхимы в норме и при патологии. Также анализируется роль факторов среды в регуляции экспрессии генов. ANNOTATION The book provides information about the role of epigenetic mechanisms in the system of monitoring renal function in normal and pathological conditions. The results of the analysis of the role of epigenetic control of gene expression of kidney transport and regulatory proteins normally indicate, firstly, the high plasticity of gene expression change processes. Secondly, they illustrate their ability to adequately respond to changes in the parameters of homeostatic functions of the kidneys, which, in turn, makes it possible to consider these processes as another element in the management of organ activity along with neuro-endocrine and intraorgan levels of the humoral control of the body's water-salt balance. The facts that emphasize the involvement of humoral factors of systemic action and intrarenal systems of humoral control in the processes of epigenetic rearrangement of the expression of renal parenchyma genes in normal and pathological conditions are presented. The role of environmental factors in the regulation of gene expression is also analyzed. Ключевые слова: почки, эпигенетика.
... The authors of the cited survey emphasize that renin expression was detected in acute myeloid leukemia blast cells, in cells of chronic myeloid leukemia and acute lymphoid leukemia. It is reported that bone marrow progenitors express renin and become the source of lymphoblastic leukemia 50 . Renin progenitors have been identified in mouse bone marrow, giving rise to B-cell leukemia 50 . ...
... It is reported that bone marrow progenitors express renin and become the source of lymphoblastic leukemia 50 . Renin progenitors have been identified in mouse bone marrow, giving rise to B-cell leukemia 50 . There are data that the renin gene expression in normal and malignant hematopoiesis can be controlled by epigenetic mechanisms 35,50 . ...
... Renin progenitors have been identified in mouse bone marrow, giving rise to B-cell leukemia 50 . There are data that the renin gene expression in normal and malignant hematopoiesis can be controlled by epigenetic mechanisms 35,50 . In the context of the topic, it is relevant to recall that complex functioning, relatively little studied, of the receptor system to the (pro) renin is relevant not only to the RAS but also to the regulation of gene expression of the protein inductor processes of inflammation and tissue fibrosis 51,52 . ...
The literature devoted to changes in the expression of the renin-angiotensin system (RAS) proteins of cancer cells was analyzed. The dynamics of RAS protein expression in malignant tumors and the possible role of epigenetic mechanisms in these processes are briefly reviewed. Through research of the epigenetic mechanisms in cancer, principally new techniques for their correction based on the use of selective regulatory systems of covalent modification of histone proteins (for example, deacetylase inhibitor) and microRNA synthesis technologies have been developed. Literature data show promising pharmacological correction of epigenetic modification of chromatin in the treatment of cancer.
