Contribution of the local RAS to hematopoietic function: a novel therapeutic target
The renin angiotensin system (RAS) has long been a known endocrine system that is involved in regulation of blood pressure and fluid balance. Over the last 2 decades, evidence has accrued that shows that there are local RAS that can affect cellular activity, tissue injury and tissue regeneration....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-10-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fendo.2013.00157/full |
| _version_ | 1818981665966391296 |
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| author | Kathleen E. Rodgers Gere S. diZerega Gere S. diZerega |
| author_facet | Kathleen E. Rodgers Gere S. diZerega Gere S. diZerega |
| author_sort | Kathleen E. Rodgers |
| collection | DOAJ |
| description | The renin angiotensin system (RAS) has long been a known endocrine system that is involved in regulation of blood pressure and fluid balance. Over the last 2 decades, evidence has accrued that shows that there are local RAS that can affect cellular activity, tissue injury and tissue regeneration. There are locally active ligand peptides, mediators, receptors and signaling pathways of the RAS in the bone marrow (BM). This system is fundamentally involved and controls the essential steps of primitive and definitive blood cell production. Hematopoiesis, erythropoiesis, myelopoiesis, thrombopoiesis, formation of monocytic and lymphocytic lineages, as well as stromal elements are regulated by the local BM RAS. The expression of a local BM RAS has been shown in very early, primitive embryonic hematopoiesis. Angiotensin-converting enzyme (ACE-1, CD143) is expressed on the surface of hemangioblasts and isolation of the CD143 positive cells allows for recovery of all hemangioblast activity, the first endothelial and hematopoietic cells, forming the marrow cavity in the embryo. CD143 expression also marks long-term blood-forming CD34+ BM cells. Expression of receptors of the RAS is modified in the BM with cellular maturation and by injury. Ligation of the receptors of the RAS has been shown to modify the status of the BM resulting in accelerated hematopoiesis after injury. The aim of the present review is to outline the known functions of the local BM RAS within the context of primitive and definitive hematopoiesis as well as modification of BM recovery by administration of exogenous ligands of the RAS. Targeting the actions of local RAS molecules could represent a valuable therapeutic option for the management of BM recovery after injury as well as neoplastic disorders. |
| first_indexed | 2024-12-20T17:34:56Z |
| format | Article |
| id | doaj.art-85953e3f8c034b9dbaed3ef453c0f5bc |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-20T17:34:56Z |
| publishDate | 2013-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-85953e3f8c034b9dbaed3ef453c0f5bc2022-12-21T19:31:14ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922013-10-01410.3389/fendo.2013.0015765288Contribution of the local RAS to hematopoietic function: a novel therapeutic targetKathleen E. Rodgers0Gere S. diZerega1Gere S. diZerega2School of Pharmacy University of Southern CaliforniaUS Biotest, Inc.Keck School of Medicine at USCThe renin angiotensin system (RAS) has long been a known endocrine system that is involved in regulation of blood pressure and fluid balance. Over the last 2 decades, evidence has accrued that shows that there are local RAS that can affect cellular activity, tissue injury and tissue regeneration. There are locally active ligand peptides, mediators, receptors and signaling pathways of the RAS in the bone marrow (BM). This system is fundamentally involved and controls the essential steps of primitive and definitive blood cell production. Hematopoiesis, erythropoiesis, myelopoiesis, thrombopoiesis, formation of monocytic and lymphocytic lineages, as well as stromal elements are regulated by the local BM RAS. The expression of a local BM RAS has been shown in very early, primitive embryonic hematopoiesis. Angiotensin-converting enzyme (ACE-1, CD143) is expressed on the surface of hemangioblasts and isolation of the CD143 positive cells allows for recovery of all hemangioblast activity, the first endothelial and hematopoietic cells, forming the marrow cavity in the embryo. CD143 expression also marks long-term blood-forming CD34+ BM cells. Expression of receptors of the RAS is modified in the BM with cellular maturation and by injury. Ligation of the receptors of the RAS has been shown to modify the status of the BM resulting in accelerated hematopoiesis after injury. The aim of the present review is to outline the known functions of the local BM RAS within the context of primitive and definitive hematopoiesis as well as modification of BM recovery by administration of exogenous ligands of the RAS. Targeting the actions of local RAS molecules could represent a valuable therapeutic option for the management of BM recovery after injury as well as neoplastic disorders.http://journal.frontiersin.org/Journal/10.3389/fendo.2013.00157/fullBone MarrowHematopoiesisStem Cellsrenin angiotensin systemmyelosuppressionprimitive |
| spellingShingle | Kathleen E. Rodgers Gere S. diZerega Gere S. diZerega Contribution of the local RAS to hematopoietic function: a novel therapeutic target Frontiers in Endocrinology Bone Marrow Hematopoiesis Stem Cells renin angiotensin system myelosuppression primitive |
| title | Contribution of the local RAS to hematopoietic function: a novel therapeutic target |
| title_full | Contribution of the local RAS to hematopoietic function: a novel therapeutic target |
| title_fullStr | Contribution of the local RAS to hematopoietic function: a novel therapeutic target |
| title_full_unstemmed | Contribution of the local RAS to hematopoietic function: a novel therapeutic target |
| title_short | Contribution of the local RAS to hematopoietic function: a novel therapeutic target |
| title_sort | contribution of the local ras to hematopoietic function a novel therapeutic target |
| topic | Bone Marrow Hematopoiesis Stem Cells renin angiotensin system myelosuppression primitive |
| url | http://journal.frontiersin.org/Journal/10.3389/fendo.2013.00157/full |
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