<i>In vivo</i> modifications of AcSDKP metabolism and haematopoiesis in mice treated with 5‐fluorouracil and Goralatide

Comte, Lydie; Lorgeot, Valérie; Bignon, Jérôme; Volkov, Léonid; Dupuis, F.; Wdzieczak‐Bakala, Joanna; Perreten, Vincent

doi:10.1046/j.1365-2362.1998.00356.x

Cited by 10 publications

(6 citation statements)

References 24 publications

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“…In the present study, we have found RENIN, ANGTS, and ACE I mRNA expressions in CD34+ stem cell samples of normal human subjects. ACE/CD143 was implicated in enhancing the recruitment of primitive stem cells into the S-phase by degrading AcSDKP [9,30,31,32,33]. ACE, converting Ang-I into Ang-II, is an important peptide for almost all aspects of hematopoiesis [23,31,34,35,36].…”

Section: Discussionmentioning

confidence: 99%

Local Renin-Angiotensin System in Normal Hematopoietic and Multiple Myeloma-Related Progenitor Cells

Tatonyan

Sayitoğlu

et al. 2014

Tjh

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Objective: The prominent functions of the local renin-angiotensin system (RAS) in primitive hematopoiesis further support the hypothesis that local autocrine bone marrow RAS could also be active in neoplastic hematopoiesis. The aim of this study is to examine critical RAS elements in normal CD34+ hematopoietic stem cells and multiple myeloma (MM)-related progenitor cells.Materials and Methods: The study group comprised the total bone marrow cells (CBM) of 10 hematologically normal people, the CD34+ stem cell samples (CD34+CBM) of 9 healthy donors for allogeneic peripheral stem cell transplantation, and the CD34+ stem cell samples (CD34+MM) of 9 MM patients undergoing autologous peripheral stem cell transplantation. We searched for the gene expression of the major RAS components in healthy hematopoietic cells and myeloma cells by quantitative real-time polymerase chain reaction analysis.Results: RENIN, angiotensinogen (ANGTS), and angiotensin converting enzyme-I (ACE I) mRNA expression levels of CBM were significantly higher than those in myeloma patients (p=0.03, p=0.002, and p=0.0008, respectively). Moreover, RENIN and ANGTS mRNA expression levels were significantly higher in CD34+ stem cell samples of healthy allogeneic donors compared to those in myeloma patients (p=0.001 and p=0.01). However, ACE I expression levels were similar in CD34+CBM and CD34+MM hematopoietic cells (p=0.89).Conclusion: Although found to be lower than in the CBM and CD34+CBM hematopoietic cells, the local RAS components were also expressed in CD34+MM hematopoietic cells. This point should be kept in mind while focusing on the immunobiology of MM and the processing of autologous cells during the formation of transplantation treatment protocols.

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Section: Discussionmentioning

confidence: 99%

Local Renin-Angiotensin System in Normal Hematopoietic and Multiple Myeloma-Related Progenitor Cells

Tatonyan

Sayitoğlu

et al. 2014

Tjh

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“…The major RAS effector agent angiotensin II (Ang II) performs its impacts on the hematopoietic system by activating the AT1Rs and AT2Rs, along with the BM microenvironment ( 11 , 12 ). As a result of ACE's (CD143) disrupting the inhibitory tetrapetide, AcSDKP, priming of stem cells into S-phase is triggered ( 16 , 21 ). Additionally, Ang-II stimulates the AT1/AT2 receptors, so it has stimulating or inhibitory effects on erythropoietin, thrombopoietin and other hematopoietic cytokines in normal hematopoiesis and myeloproliferative diseases ( 16 , 22 , 23 ).…”

Section: Local Bone Marrow Renin Angiotensin System: Definition and Amentioning

confidence: 99%

Pathobiological Interactions of Local Bone Marrow Renin-Angiotensin System and Central Nervous System in Systemic Arterial Hypertension

Çiftçiler

Haznedaroğlu

2020

Front. Endocrinol.

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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.

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“…Therefore ACE hyperfunction may lead to the acceleration of AcSDKP metabolism, which in turn would lower its levels in the BM microenvironment, finally removing the antiproliferative effects of the peptide on haematopoietic cells and blasts. The haemoregulatory tetrapeptide AcSDKP reversibly prevents the recruitment of pluripotent HSCs and normal early haematopoietic progenitors into S-phase of the cell cycle by keeping them quiescent [14,16,34].…”

Section: Reference Evidence Proposalmentioning

confidence: 99%

“…ACE hyperfunction results in faster hydrolysis of the AcSDKP peptide, which in turn decreases in BM tissues, allowing HSCs to enter the S-stage of the cell cycle [4,16,34]. The plasma concentration of AcSDKP, a reversible negative regulator of the proliferation of normal haematopoietic stem cells, is physiologically regulated by ACE [14][15][16]121]. In vitro incubation of AML cells with an ACEI decreased the growth and colony-forming ability of AML cells in a dose-dependent manner.…”

Section: Acementioning

confidence: 99%

“…The major RAS effector mediator AngII (angiotensin II) exerts its haematopoietic effects by activating angiotensin receptors, primarily AT 1 Rs and AT 2 Rs, within the BM micro-environment [4,5]. ACE (CD143) has been implicated in enhancing the recruitment of primitive stem cells into S-phase by degrading AcSDKP [9,[14][15][16][17]. Moreover, stimulation of AT 1 Rs/AT 2 Rs by AngII, the principle effector molecule of the RAS, exerts stimulatory/inhibitory action on the JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway, which is directly linked to the physiological functions of erythropoietin, thrombopoietin and other haematopoietic cytokines during normal haematopoiesis and in myeloproliferative neoplasms [9,[18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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Local bone marrow renin–angiotensin system in primitive, definitive and neoplastic haematopoiesis

Haznedaroğlu

Beyazıt

2012

Clinical Science

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The locally active ligand peptides, mediators, receptors and signalling pathways of the haematopoietic BM (bone marrow) autocrine/paracrine RAS (renin-angiotensin system) affect the essential steps of definitive blood cell production. Haematopoiesis, erythropoiesis, myelopoiesis, formation of monocytic and lymphocytic lineages, thrombopoiesis and other stromal cellular elements are regulated by the local BM RAS. The local BM RAS is present and active even in primitive embryonic haematopoiesis. ACE (angiotensin-converting enzyme) is expressed on the surface of the first endothelial and haematopoietic cells, forming the marrow cavity in the embryo. ACE marks early haematopoietic precursor cells and long-term blood-forming CD34(+) BM cells. The local autocrine tissue BM RAS may also be active in neoplastic haematopoiesis. Critical RAS mediators such as renin, ACE, AngII (angiotensin II) and angiotensinogen have been identified in leukaemic blast cells. The local tissue RAS influences tumour growth and metastases in an autocrine and paracrine fashion via the modulation of numerous carcinogenic events, such as angiogenesis, apoptosis, cellular proliferation, immune responses, cell signalling and extracellular matrix formation. The aim of the present review is to outline the known functions of the local BM RAS within the context of primitive, definitive and neoplastic haematopoiesis. Targeting the actions of local RAS molecules could represent a valuable therapeutic option for the management of neoplastic disorders.

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In vivo modifications of AcSDKP metabolism and haematopoiesis in mice treated with 5‐fluorouracil and Goralatide

Abstract: By improving our knowledge of the biology of AcSDKP in vivo during chemotherapy, our results could help to better define the therapeutic use of Goralatide.

Cited by 10 publications

References 24 publications

Local Renin-Angiotensin System in Normal Hematopoietic and Multiple Myeloma-Related Progenitor Cells

Local Renin-Angiotensin System in Normal Hematopoietic and Multiple Myeloma-Related Progenitor Cells

Pathobiological Interactions of Local Bone Marrow Renin-Angiotensin System and Central Nervous System in Systemic Arterial Hypertension

Local bone marrow renin–angiotensin system in primitive, definitive and neoplastic haematopoiesis

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