ArticleThe Journal of experimental medicine2013
Erythropoietin-directed erythropoiesis depends on serpin inhibition of erythroblast lysosomal cathepsins.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
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- Mitochondrial retention and autophagy dysregulation drive oxidative stress in sickle cell disease erythrocytes.Experimental hematology · 2025Article
- Cell death signaling in human erythron: erythrocytes lose the complexity of cell death machinery upon maturation.Apoptosis : an international journal on programmed cell death · 2025Review
- Cytosolic serpins act in a cytoprotective feedback loop that limits ESX-1-dependent death ofmBio · 2024Article
- NNature communications · 2023Article
- Article
- Phospho-PTM proteomic discovery of novel EPO- modulated kinases and phosphatases, including PTPN18 as a positive regulator of EPOR/JAK2 Signaling.Cellular signalling · 2020Article
- Phospho-proteomic discovery of novel signal transducers including thioredoxin-interacting protein as mediators of erythropoietin-dependent human erythropoiesis.Experimental hematology · 2020Article
- Erythropoietin regulation of red blood cell production: from bench to bedside and back.F1000Research · 2020Review
- Antiapoptotic serine protease inhibitors contribute to survival of allergenic TThe Journal of allergy and clinical immunology · 2018Article
- Iron modulation of erythropoiesis is associated with Scribble-mediated control of the erythropoietin receptor.The Journal of experimental medicine · 2018Article
- Non-apoptotic functions of caspases in myeloid cell differentiation.Cell death and differentiation · 2017Review
- Governing roles for Trib3 pseudokinase during stress erythropoiesis.Experimental hematology · 2017Article
- Targeting EPO and EPO receptor pathways in anemia and dysregulated erythropoiesis.Expert opinion on therapeutic targets · 2016Review
- Review
- Brief report: serpin Spi2A as a novel modulator of hematopoietic progenitor cell formation.Stem cells (Dayton, Ohio) · 2014Article
- RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development.The Journal of experimental medicine · 2014Article
- Article
- Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration.The Journal of experimental medicine · 2013Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Erythropoietin (EPO) and its cell surface receptor (EPOR) are essential for red blood cell production and exert important cytoprotective effects on select vascular, immune, and cancer cells. To discover novel EPO action modes, we profiled the transcriptome of primary erythroid progenitors. We report Serpina3g/Spi2A as a major new EPO/EPOR target for the survival of erythroid progenitors. In knockout mice, loss of Spi2A worsened anemia caused by hemolysis, radiation, or transplantation. EPO-induced erythropoiesis also was compromised. In particular, maturing erythroblasts required Spi2A for cytoprotection, with iron and reactive oxygen species as cytotoxic agents. Spi2A defects were ameliorated by cathepsin-B/L inhibition, and by genetic co-deletion of lysosomal cathepsin B. Pharmacological inhibition of cathepsin B/L enhanced EPO-induced red cell formation in normal mice. Overall, we define an unexpected EPO action mode via an EPOR-Spi2A serpin-cathepsin axis in maturing erythroblasts, with lysosomal cathepsins as novel therapeutic targets.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.