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Stimulating erythropoiesis in inflammatory bowel disease associated anemia

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World Journal of Gastroenterology 2007年第36期13卷 4798-4806页

作者： Georgia Tsiolakidou Ioannis E Koutroubakis Department of Gastroenterology University Hospital Heraklion Crete Greece

Anemia is a frequent complication in patients with inflammatory bowel disease (IBD), and is associated with decreased quality of life and increased rate of hospitalization. The primary therapeutic targets of IBD- associated anemia are iron deficiency and anemia of chronic disease. An important prognostic parameter of the success or failure of therapy is the outcome of the underlying disease. Iron deficiency should be appropriately managed with iron supplementation. However, the use of oral iron therapy is limited by several problems, the most important being gastrointestinal side effects leading occasionally to disease relapse and poor iron absorption. Intravenous iron preparations are more reliable, with iron sucrose demonstrating the best efficacy and tolerability. Treatment with erythropoietin or darbepoetin has been proven to be effective in patients with anemia, who fail to respond to intravenous iron. Patients with ongoing inflammation have anemia of chronic disease and may require combination therapy comprising of intravenous iron sucrose and erythropoietin. After initiating treatment, careful monitoring of hemoglobin levels and iron parameters is needed in order to avoid recurrence of anemia. In conclusion, anemia in the setting of IBD should be aggressively diagnosed, investigated, and treated. Future studies should define the optimal dose and schedule of intravenous iron supplementation and appropriate erythropoietin therapy in these patients.

关键词： Anemia Crohn’s disease erythropoiesis Erythropoietin Iron Ulcerative colitis

Crosstalk between catecholamines and erythropoiesis

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Frontiers in Biology 2017年第2期12卷 103-115页

作者： Fakhredin Saba Najmaldin Saki Elahe Khodadi Masoud Soleimani Department of Laboratory Science Kermanshah University of Medical Sciences Kermanshah Iran Department of Hematology Faculty of Medical Sciences Tarbiat Modares University Tehran Iran Health Research Institute Research Center of Thalassemia & Hemoglobinopathy Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran

BACKGROUND： erythropoiesis is regulated by a range of intrinsic and extrinsic factors, including different cytokines. Recently, the role of catecholamines has been highlighted in the development of erythroid cell lineages. OBJECTIVE： This study focuses on the biological links interconnecting erythroid development and the sympathetic nervous system. The emerging evidence that underscores the role of catecholamines in the regulation of erythropoietin and other erythropoiesis cytokines are thoroughly reviewed, in addition to elements such as iron and the leptin hormone that are involved in erythropoiesis. METHODS： Relevant English-language studies were identified and retrieved from the PubMed search engine （1981-2017） using the following keywords：＂erythropoiesis＂, ＂Catecholamines＂, ＂Nervous system＂, and ＂Cytokines.＂ RESULTS： Chronic social stress alters and suppresses erythroid development. However, the physiological release of catecholamines is an additional stimulator of erythropoiesis in the setting of anemia. Therefore, the severity and timing of catecholamine secretion might distinctly regulate erythroid homeostasis. CONCLUSION： Understanding the relationship of catecholamines with different elements of the erythroid islands will be essential to find the tightly regulated production of red blood cells （RBCs） in both chronic and physiological catecholamine activation.

关键词： erythropoiesis cytokines catecholamines chronic social stress nervous system

MicroRNAs in erythropoiesis and red blood cell disorders

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Frontiers in Biology 2015年第4期10卷 321-332页

作者： Javad Mohammdai-asl Abolfazl Ramezani Fatemeh Norozi Amal Saki Malehi Ali Amin Asnafi Mohammad Ali Jalali Far Seyed Hadi Mousavi Najmaldin Saki Department of Medical Genetics Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran Healthresearch Institute Research Center of Thalassemia & Hemoglobinopathy Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran Department of Biostatistics and Epidemiology School of Public Health Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran Hematology Department Allied Medical School Tehran University of Medical Sciences Tehran Iran

MicroRNAs （miRNAs） are 19-24 nucleotide non-coding ribonucleic acids binding DNA or RNA and controlling gene expression via mRNA degradation or its transcription inhibition. Erythropoies is a multi step differentiation process of erythroid progenitors to nucleate red blood cells. Maturation, proliferation and differentiation of red blood cells is affected by erythroid factors, signaling pathways in niche of hematopoietic cells, transcription factors as well as miRNAs. Expression of different types of miRNAs during erythroid development provides a background for the study of these molecules to control erythroid differentiation and maturation as well as their use as diagnostic and prognostic markers to treat erythroid disorders like thalassemia, sickle cell disease and erythrocyte enzyme deficiencies. In this paper, with reference to biosynthesis of miRNAs, their function in normal and anemic erythropoiesis has been investigated. The target molecule of each of these miRNAs has been cited in an attempt to elucidate their role in erythropoiesis.

关键词： miRNA erythropoiesis red blood cell

Cell *** roles of p19INK4d in human terminal erythropoiesis

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Chinese Journal of Cancer 2017年第4期36卷 163-164页

作者： Xu Han Jing Liu The State Key Laboratory of Medical Genetics & School of Life Sciences Central South University Changsha 410078 Hunan P. R. China

Normally, cyclin interacts with cyclin-dependent kinase (CDK) to form a cyclin-CDK complex, which promotes cell cycle progression, whereas cyclin-dependent kinase inhibitor (CDKI) molecules inhibit the formation of cyclin- CDK complex, arresting cell cycle. Terminal erythropoiesis is closely coordinated with cell cycle exit, which is regulated by cyclins, CDKs, and CDKIs [1]. In the global transcriptome of human terminal erythropoiesis [2], p19INK4d is expressed highly, and its expression is significantly up-regulated during human terminal erythropoiesis. However, the roles of p19INK4d in terminal erythropoiesis are still unknown.

关键词： roles erythropoiesis CDK

Zebrafish ELL-associated factors Eaf1/2 modulate erythropoiesis via regulating gata1a expression and WNT signaling to facilitate hypoxia tolerance

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Cell Regeneration 2023年第1期12卷 295-312页

作者： WenYe Liu ShuHui Lin LingYa Li ZhiPeng Tai Jing-Xia Liu College of Fisheries Key Laboratory of Freshwater Animal BreedingMinistry of AgricultureHuazhong Agricultural University430070 WuhanChina

EAF1 and EAF2,the eleven-nineteen lysine-rich leukemia(ELL)-associated factors which can assemble to the super elongation complex(AFF1/4,AF9/ENL,ELL,and P-TEFb),are reported to participate in RNA polymeraseⅡto actively regulate a variety of biological processes,including leukemia and embryogenesis,but whether and how EAF1/2 function in hematopoietic system related hypoxia tolerance during embryogenesis remains ***,we unveiled that deletion of EAF1/2(eaf1^(-/-)and eaf2^(-/-))caused reduction in hypoxia tolerance in zebrafish,leading to reduced erythropoiesis during hematopoietic ***,eaf1^(-/-)and eaf2^(-/-)mutants showed significant reduc-tion in the expression of key transcriptional regulators scl,lmo2,and gata1a in erythropoiesis at both 24 h post fertilization(hpf)and 72 hpf,with gata1a downregulated while scl and lmo2 upregulated at 14 ***,eaf1^(-/-)and eaf2^(-/-)mutants exhibited significant changes in the expression of epigenetic modified histones,with a significant increase in the binding enrichment of modified histone H3K27me3 in gata1a promoter rather than scl and lmo2 ***,eaf1^(-/-)and eaf2^(-/-)mutants exhibited a dynamic expression of canonical WNT/β-catenin signaling during erythropoiesis,with significant reduction in p-β-Catenin level and in the binding enrichment of both scl and lmo2 promoters with the WNT transcriptional factor TCF4 at 24 *** findings demonstrate an important role of Eaf1/2 in erythropoiesis in zebrafish and may have shed some light on regeneration medicine for anemia and related diseases and on molecular basis for fish economic or productive traits,such as growth,disease resistance,hypoxia tolerance,and so on.

关键词： EAF1/2 gata1a/scl/lmo2 erythropoiesis H3K27me3 WNT/β-Catenin signaling TCF4

erythropoiesis Stimulating Agents (ESAs) in the Treatment of Cardio-Renal Syndrome Anaemia

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Open Journal of Nephrology 2012年第3期2卷 23-28页

作者： Ioannis Koulouridis Efstathios Koulouridis Department of Nephrology General Hospital of Corfu Greece

Coexistence of chronic kidney disease (CKD) and chronic heart failure (CHF) define a recently recognized clinical entity known as cardio-renal syndrome. Sufficient evidence suggests that the two pathological conditions share common pathogenic etiology which is not yet fully defined. Superimposed anaemia is a common finding among patients suffering from cardio-renal syndrome. The combination of CKD, CHF and anaemia increase the probability of death by 6 times compared to normal individuals. Early attempts to restore anaemia either by iron supplementation, erythropoiesis stimulating agents (ESAs) or combination of the two have reported to improve quality of life, morbidity and mortality especially among patients treated by cardiologists. Recent publications of well controlled epidemiological studies failed to prove convincing beneficial effect of the above mentioned therapy moreover skepticism has raised concerning the safety of restoring anaemia among patients with cardio-renal syndrome as well as used medications. There are still unresolved problems concerning the definition of anaemia, by means of hemoglobin level among these patients, the target hemoglobin level and the therapeutic regimen of ESAs administration and iron supplementation. We need much more evidence in order to define an effective and safe treatment strategy correcting anaemia among patients with cardio-renal syndrome.

关键词： Cardio-Renal Syndrome Anaemia erythropoiesis Stimulating Agents Adverse Outcomes

Iron-Restricted erythropoiesis in Anaemic Patients with Giant Cell Arteritis and Polymyalgia Rheumatica

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Open Journal of Blood Diseases 2013年第1期3卷 49-52页

作者： Torbjorn Karlsson Department of Haematology Uppsala University HospitalUppsalaSweden.

The aim of this observational study was to biochemically characterize the anaemia in GCA (giant cell arteritis) and PMR (polymyalgia rheumatica) patients. Values for mean corpuscular volume, mean corpuscular hemoglobin and soluble transferrin receptor were normal, whereas serum iron and total iron binding capacity (TIBC) were subnormal, and mean ferritin was above the upper reference limit. Iron-restricted erythropoiesis (IRE), defined as a bone marrow smear staining positive for iron in combination with transferrin saturation less than 20%, was present in all patients. All patients exhibited clinical and biochemical signs of active inflammation with elevated C-reactive protein and an increased erythrocyte sedimentation rate.

关键词： Anaemia Iron-Restriction erythropoiesis Giant Cell Arteritis Polymyalgia Rheumatica

Post-transcriptional regulation of erythropoiesis

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Blood Science 2023年第3期5卷 150-159页

作者： Yanan Li Haihang Zhang Bin Hu Pan Wang Wei Wang Jing Liu Molecular Biology Research Center Hunan Province Key Laboratory of Basic and Applied HematologySchool of Life SciencesCentral South UniversityChangshaHunan 410078China Department of Imaging and Interventional Radiology The Third Xiangya Hospital of Central South UniversityChangshaHunanChina

erythropoiesis is a complex,precise,and lifelong process that is essential for maintaining normal body *** strict regulation is necessary to prevent a variety of blood *** erythropoiesis is precisely regulated by an intricate network that involves transcription levels,signal transduction,and various epigenetic *** recent years,research on posttranscriptional levels in erythropoiesis has expanded *** dynamic regulation of splicing transitions is responsible for changes in protein isoform expression that add new functions beneficial for ***-binding proteins adapt the translation of transcripts to the protein requirements of the cell,yielding mRNA with dynamic translation *** RNAs,such as microRNAs and lncRNAs,are indispensable for changing the translational efficiency and/or stability of targeted mRNAs to maintain the normal expression of genes related to erythropoiesis.N6-methyladenosine-dependent regulation of mRNA translation plays an important role in maintaining the expression programs of erythroid-related genes and promoting erythroid lineage *** review aims to describe our current understanding of the role of post-transcriptional regulation in erythropoiesis and erythroid-associated diseases,and to shed light on the physiological and pathological implications of the post-transcriptional regulation machinery in *** may help to further enrich our understanding of the regulatory network of erythropoiesis and provide new strategies for the diagnosis and treatment of erythroid-related diseases.

关键词： erythropoiesis mRNA stability Noncoding RNA Post-transcriptional regulation

Long non-coding RNAs during normal erythropoiesis

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Blood Science 2019年第2期1卷 137-140页

作者： Changlu Xu Lihong Shi State Key Laboratory of Experimental Hematology National Clinical Research Center for Hematological DisordersInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjinChina Center for Stem Cell Medicine Chinese Academy of Medical Sciences&Department of Stem Cells and Regenerative MedicinePeking Union Medical CollegeTianjinChina

The transcription of essentially the entire eukaryotic genome produces a huge amount of non-coding *** them,long noncoding RNAs(lncRNAs)consist of a significant portion that widely exists across mammal genome,generating from high-throughput transcriptomic studies in the last *** the functions of most lncRNAs remain to be further investigated,many of them have already been shown to play critical roles during normal development and disease *** evidence indicates that lncRNAs involve in versatile biological processes during erythroid proliferation and differentiation,including erythroid cell survival,heme metabolism,globin switching and regulation,erythroid enucleation,etc,via cis-or trans-mediated molecular *** this review,we focus on recent advances regarding the functions and mechanisms of lncRNAs in normal erythropoiesis.

关键词： erythropoiesis Globin regulation Heme biosynthesis Long non-coding RNAs