Correction of Anemia in Chronic Kidney Disease With Angelica sinensis Polysaccharide via Restoring EPO Production and Improving Iron Availability

Given the limited efficacy and potential disadvantages of erythropoiesis-stimulating agents (ESAs) in treating anemia of chronic kidney disease (CKD), the development of better alternative therapies has become a priority. The primary purpose of this study is to investigate the effects of Angelica si...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Kaiping Wang [verfasserIn] Jun Wu [verfasserIn] Jingya Xu [verfasserIn] Saisai Gu [verfasserIn] Qiang Li [verfasserIn] Peng Cao [verfasserIn] Mingming Li [verfasserIn] Yu Zhang [verfasserIn] Fang Zeng [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	anemia chronic kidney disease erythropoietin iron polysaccharide

Übergeordnetes Werk:	In: Frontiers in Pharmacology - Frontiers Media S.A., 2010, 9(2018)
Übergeordnetes Werk:	volume:9 ; year:2018

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fphar.2018.00803

Katalog-ID:	DOAJ031900836

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520			\|a Given the limited efficacy and potential disadvantages of erythropoiesis-stimulating agents (ESAs) in treating anemia of chronic kidney disease (CKD), the development of better alternative therapies has become a priority. The primary purpose of this study is to investigate the effects of Angelica sinensis polysaccharide (ASP) and its underlying mechanism in the treatment of renal anemia. In the present study, we found that ASP could enhance hypoxic induction of EPO in Hep3B cells, with a mechanism that involved the stabilization of HIF-2α protein. In parallel, ASP rescued the inhibition of EPO, induced by proinflammatory factor TNF-α through blocking GATA2 and NF-κB activation. In a rat model of adenine-induced anemia of CKD, oral administration of ASP corrected anemia and alleviated renal damage and inflammation. By increasing the accumulation of HIF-2α protein and reducing the expression of NF-κB and GATA2 as well as pro-inflammatory cytokines, ASP stimulated both renal and hepatic EPO production, and resulted in an elevation of serum EPO. The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats. Furthermore, we found that ASP suppressed hepatic hepcidin expression, mobilized iron from spleen and liver and increased serum iron. These findings demonstrate that ASP elicits anti-anemic action by restoring EPO production and improving iron availability in the setting of CKD in rats.
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allfieldsSound	10.3389/fphar.2018.00803 doi (DE-627)DOAJ031900836 (DE-599)DOAJ53c971c34735476a8116b255f074a564 DE-627 ger DE-627 rakwb eng RM1-950 Kaiping Wang verfasserin aut Correction of Anemia in Chronic Kidney Disease With Angelica sinensis Polysaccharide via Restoring EPO Production and Improving Iron Availability 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Given the limited efficacy and potential disadvantages of erythropoiesis-stimulating agents (ESAs) in treating anemia of chronic kidney disease (CKD), the development of better alternative therapies has become a priority. The primary purpose of this study is to investigate the effects of Angelica sinensis polysaccharide (ASP) and its underlying mechanism in the treatment of renal anemia. In the present study, we found that ASP could enhance hypoxic induction of EPO in Hep3B cells, with a mechanism that involved the stabilization of HIF-2α protein. In parallel, ASP rescued the inhibition of EPO, induced by proinflammatory factor TNF-α through blocking GATA2 and NF-κB activation. In a rat model of adenine-induced anemia of CKD, oral administration of ASP corrected anemia and alleviated renal damage and inflammation. By increasing the accumulation of HIF-2α protein and reducing the expression of NF-κB and GATA2 as well as pro-inflammatory cytokines, ASP stimulated both renal and hepatic EPO production, and resulted in an elevation of serum EPO. The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats. Furthermore, we found that ASP suppressed hepatic hepcidin expression, mobilized iron from spleen and liver and increased serum iron. These findings demonstrate that ASP elicits anti-anemic action by restoring EPO production and improving iron availability in the setting of CKD in rats. anemia chronic kidney disease erythropoietin iron polysaccharide Therapeutics. Pharmacology Jun Wu verfasserin aut Jingya Xu verfasserin aut Saisai Gu verfasserin aut Qiang Li verfasserin aut Peng Cao verfasserin aut Mingming Li verfasserin aut Yu Zhang verfasserin aut Fang Zeng verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 9(2018) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:9 year:2018 https://doi.org/10.3389/fphar.2018.00803 kostenfrei https://doaj.org/article/53c971c34735476a8116b255f074a564 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2018.00803/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
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authorswithroles_txt_mv	Kaiping Wang @@aut@@ Jun Wu @@aut@@ Jingya Xu @@aut@@ Saisai Gu @@aut@@ Qiang Li @@aut@@ Peng Cao @@aut@@ Mingming Li @@aut@@ Yu Zhang @@aut@@ Fang Zeng @@aut@@
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callnumber-first	R - Medicine
author	Kaiping Wang
spellingShingle	Kaiping Wang misc RM1-950 misc anemia misc chronic kidney disease misc erythropoietin misc iron misc polysaccharide misc Therapeutics. Pharmacology Correction of Anemia in Chronic Kidney Disease With Angelica sinensis Polysaccharide via Restoring EPO Production and Improving Iron Availability
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topic_title	RM1-950 Correction of Anemia in Chronic Kidney Disease With Angelica sinensis Polysaccharide via Restoring EPO Production and Improving Iron Availability anemia chronic kidney disease erythropoietin iron polysaccharide
topic	misc RM1-950 misc anemia misc chronic kidney disease misc erythropoietin misc iron misc polysaccharide misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc anemia misc chronic kidney disease misc erythropoietin misc iron misc polysaccharide misc Therapeutics. Pharmacology
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title	Correction of Anemia in Chronic Kidney Disease With Angelica sinensis Polysaccharide via Restoring EPO Production and Improving Iron Availability
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title_full	Correction of Anemia in Chronic Kidney Disease With Angelica sinensis Polysaccharide via Restoring EPO Production and Improving Iron Availability
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title_sort	correction of anemia in chronic kidney disease with angelica sinensis polysaccharide via restoring epo production and improving iron availability
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title_auth	Correction of Anemia in Chronic Kidney Disease With Angelica sinensis Polysaccharide via Restoring EPO Production and Improving Iron Availability
abstract	Given the limited efficacy and potential disadvantages of erythropoiesis-stimulating agents (ESAs) in treating anemia of chronic kidney disease (CKD), the development of better alternative therapies has become a priority. The primary purpose of this study is to investigate the effects of Angelica sinensis polysaccharide (ASP) and its underlying mechanism in the treatment of renal anemia. In the present study, we found that ASP could enhance hypoxic induction of EPO in Hep3B cells, with a mechanism that involved the stabilization of HIF-2α protein. In parallel, ASP rescued the inhibition of EPO, induced by proinflammatory factor TNF-α through blocking GATA2 and NF-κB activation. In a rat model of adenine-induced anemia of CKD, oral administration of ASP corrected anemia and alleviated renal damage and inflammation. By increasing the accumulation of HIF-2α protein and reducing the expression of NF-κB and GATA2 as well as pro-inflammatory cytokines, ASP stimulated both renal and hepatic EPO production, and resulted in an elevation of serum EPO. The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats. Furthermore, we found that ASP suppressed hepatic hepcidin expression, mobilized iron from spleen and liver and increased serum iron. These findings demonstrate that ASP elicits anti-anemic action by restoring EPO production and improving iron availability in the setting of CKD in rats.
abstractGer	Given the limited efficacy and potential disadvantages of erythropoiesis-stimulating agents (ESAs) in treating anemia of chronic kidney disease (CKD), the development of better alternative therapies has become a priority. The primary purpose of this study is to investigate the effects of Angelica sinensis polysaccharide (ASP) and its underlying mechanism in the treatment of renal anemia. In the present study, we found that ASP could enhance hypoxic induction of EPO in Hep3B cells, with a mechanism that involved the stabilization of HIF-2α protein. In parallel, ASP rescued the inhibition of EPO, induced by proinflammatory factor TNF-α through blocking GATA2 and NF-κB activation. In a rat model of adenine-induced anemia of CKD, oral administration of ASP corrected anemia and alleviated renal damage and inflammation. By increasing the accumulation of HIF-2α protein and reducing the expression of NF-κB and GATA2 as well as pro-inflammatory cytokines, ASP stimulated both renal and hepatic EPO production, and resulted in an elevation of serum EPO. The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats. Furthermore, we found that ASP suppressed hepatic hepcidin expression, mobilized iron from spleen and liver and increased serum iron. These findings demonstrate that ASP elicits anti-anemic action by restoring EPO production and improving iron availability in the setting of CKD in rats.
abstract_unstemmed	Given the limited efficacy and potential disadvantages of erythropoiesis-stimulating agents (ESAs) in treating anemia of chronic kidney disease (CKD), the development of better alternative therapies has become a priority. The primary purpose of this study is to investigate the effects of Angelica sinensis polysaccharide (ASP) and its underlying mechanism in the treatment of renal anemia. In the present study, we found that ASP could enhance hypoxic induction of EPO in Hep3B cells, with a mechanism that involved the stabilization of HIF-2α protein. In parallel, ASP rescued the inhibition of EPO, induced by proinflammatory factor TNF-α through blocking GATA2 and NF-κB activation. In a rat model of adenine-induced anemia of CKD, oral administration of ASP corrected anemia and alleviated renal damage and inflammation. By increasing the accumulation of HIF-2α protein and reducing the expression of NF-κB and GATA2 as well as pro-inflammatory cytokines, ASP stimulated both renal and hepatic EPO production, and resulted in an elevation of serum EPO. The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats. Furthermore, we found that ASP suppressed hepatic hepcidin expression, mobilized iron from spleen and liver and increased serum iron. These findings demonstrate that ASP elicits anti-anemic action by restoring EPO production and improving iron availability in the setting of CKD in rats.
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title_short	Correction of Anemia in Chronic Kidney Disease With Angelica sinensis Polysaccharide via Restoring EPO Production and Improving Iron Availability
url	https://doi.org/10.3389/fphar.2018.00803 https://doaj.org/article/53c971c34735476a8116b255f074a564 https://www.frontiersin.org/article/10.3389/fphar.2018.00803/full https://doaj.org/toc/1663-9812
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The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats. Furthermore, we found that ASP suppressed hepatic hepcidin expression, mobilized iron from spleen and liver and increased serum iron. 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Correction of Anemia in Chronic Kidney Disease With Angelica sinensis Polysaccharide via Restoring EPO Production and Improving Iron Availability

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