Exposure to hypoxia causes stress erythropoiesis and downregulates immune response genes in spleen of mice

Wang, Haijing; Liu, Daoxin; Song, Pengfei; Jiang, Feng; Chi, Xiaowei; Zhang, Tongzuo

doi:10.1186/s12864-021-07731-x

Cited by 21 publications

(23 citation statements)

References 79 publications

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“…5E-F). Together, our results for the first time show that during localized L. major infection, iron content within spleen remains unaltered, however, the expression of erythroid related genes increased abruptly which has already been recognized as the stress erythropoiesis response in mice (Liao et al, 2018;H. Wang et al, 2021).…”

Section: Major Infection Causes Splenomegaly and Triggers Extramedull...supporting

confidence: 57%

Localized Leishmania major infection causes systemic iron deficiency that can be controlled by oral iron supplementation

Banerjee

Datta

2022

Preprint

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Leishmania major (L. major) and its related parasitic species infection causes human cutaneous leishmaniasis that results into disfiguring skin lesion. Although L. major infection has been found to alter macrophage iron homeostasis we have limited understanding on whether it can also manipulate the same at systemic level. In fact, localized L. major infection found to promote iron deficiency anemia in children by an unknown mechanism. To address these unresolved issues, Balb/c mouse were infected with L. major and iron status in different organs were monitored systematically with the development of cutaneous lesion. At week 10 post infection when there was maximum lesion development in the parasite infected left hind footpad, the iron content increased significantly in this tissue with the concomitant increase in parasite burden. L. major infection mediated iron accumulation in infected mouse footpad was found to be due to transferrin receptor upregulation and natural resistance-associated macrophage protein 1 (Nramp1) downregulation. Surge in iron level was found to be associated with the reduced hepatic iron storage that resulted increased serum iron. Limited iron storage in liver and bone-marrow of infected mice caused reduced hemoglobin level and production of deformed erythrocytes. Interestingly, L. major infected mice developed splenomegaly with significant upregulation of erythroid related genes. Importantly, oral iron supplementation post infection rescued the development of cutaneous lesion in infected mice. Together, our study unravelled a comprehensive mechanism behind developing iron deficiency anemia during cutaneous leishmaniasis and a novel therapeutic route of treating this infection by delivering iron.

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Section: Major Infection Causes Splenomegaly and Triggers Extramedull...supporting

confidence: 57%

Localized Leishmania major infection causes systemic iron deficiency that can be controlled by oral iron supplementation

Banerjee

Datta

2022

Preprint

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“…To divide highly co-occurred OTUs into several module members, hierarchical clustering using the dynamic tree cut method with DeepSplit of 3 was performed to create a hierarchical clustering tree of OTUs as a dendrogram ( Do et al, 2017 ). Module eigengenes were calculated using the moduleEigengenes() function in the WGCNA R package to demonstrate the correlation of the module eigenvalue and OTU abundance profile ( Wang et al, 2021 ). Then, we identified potential modules and OTUs associated with season, age, and gender.…”

Section: Methodsmentioning

confidence: 99%

Marked Seasonal Variation in Structure and Function of Gut Microbiota in Forest and Alpine Musk Deer

et al. 2021

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Musk deer (Moschus spp.) is a globally endangered species due to excessive hunting and habitat fragmentation. Captive breeding of musk deer can efficiently relieve the hunting pressure and contribute to the conservation of the wild population and musk supply. However, its effect on the gut microbiota of musk deer is unclear. Recent studies have indicated that gut microbiota is associated with host health and its environmental adaption, influenced by many factors. Herein, high-throughput sequencing of the 16S rRNA gene was used based on 262 fecal samples from forest musk deer (M. berezovskii) (FMD) and 90 samples from alpine musk deer (M. chrysogaster) (AMD). We sought to determine whether seasonal variation can affect the structure and function of gut microbiota in musk deer. The results demonstrated that FMD and AMD had higher α-diversity of gut microbiota in the cold season than in the warm season, suggesting that season change can affect gut microbiota diversity in musk deer. Principal coordinate analysis (PCoA) also revealed significant seasonal differences in the structure and function of gut microbiota in AMD and FMD. Particularly, phyla Firmicutes and Bacteroidetes significantly dominated the 352 fecal samples from captive FMD and AMD. The relative abundance of Firmicutes and the ratio of Firmicutes to Bacteroidetes were significantly decreased in summer than in spring and substantially increased in winter than in summer. In contrast, the relative abundance of Bacteroidetes showed opposite results. Furthermore, dominant bacterial genera and main metabolic functions of gut microbiota in musk deer showed significant seasonal differences. Overall, the abundance of main gut microbiota metabolic functions in FMD was significantly higher in the cold season. WGCNA analysis indicated that OTU6606, OTU5027, OTU7522, and OTU3787 were at the core of the network and significantly related with the seasonal variation. These results indicated that the structure and function in the gut microbiota of captive musk deer vary with seasons, which is beneficial to the environmental adaptation and the digestion and metabolism of food. This study provides valuable insights into the healthy captive breeding of musk deer and future reintroduction programs to recover wild populations.

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“…Animal models have been crucial to the advances in understanding the mechanisms of SE activation and regulation ( Lenox et al, 2005 ; Millot et al, 2010 ; Ulyanova et al, 2016 ; Vignjević Petrinović et al, 2020 ). Accumulating data from different mouse models suggest that, unlike steady-state erythropoiesis, Hedgehog and BMP4 signaling along with glucocorticoids, EPO, SCF, GDF15 and hypoxia-inducible factors plays a pivotal role in SE ( Perry et al, 2009 ; Millot et al, 2010 ; Voorhees et al, 2013 ; Vignjević et al, 2014 ; Hao et al, 2019 ; Wang et al, 2021 ). The activation of the glucocorticoid receptor is essential for the expansion of immature erythroid cells during SE ( Bauer et al, 1999 ; Vignjevic et al, 2015 ) and it seems that glucocorticoids act synergistically with hypoxia-inducible factor-1 alpha (HIF-1α)and GDF15 to promote rapid proliferation of stress erythroid progenitors whose self-renewal is critically dependent on BMP4 signaling ( Flygare et al, 2011 ; Hao et al, 2019 ).…”

Section: Evolving Concepts Of Stress Erythropoiesismentioning

confidence: 99%

“…Furthermore, during SE, the expression of BMP4 is delayed in the spleens of flexed-tail (f/f) mutant mice, which have a mutant SMAD5 with the ability to also inhibit the function of SMAD1 and 8, suggesting that SMAD1/5/8 may act concordantly with HIF-2α to regulate transcription of BMP4 in the spleen under SE conditions. Additionally, new evidence suggests that HIF-3α might be involved in SE as well ( Wang et al, 2021 ).…”

Section: Evolving Concepts Of Stress Erythropoiesismentioning

confidence: 99%

Targeting Stress Erythropoiesis Pathways in Cancer

et al. 2022

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Cancer-related anemia (CRA) is a common multifactorial disorder that adversely affects the quality of life and overall prognosis in patients with cancer. Safety concerns associated with the most common CRA treatment options, including intravenous iron therapy and erythropoietic-stimulating agents, have often resulted in no or suboptimal anemia management for many cancer patients. Chronic anemia creates a vital need to restore normal erythropoietic output and therefore activates the mechanisms of stress erythropoiesis (SE). A growing body of evidence demonstrates that bone morphogenetic protein 4 (BMP4) signaling, along with glucocorticoids, erythropoietin, stem cell factor, growth differentiation factor 15 (GDF15) and hypoxia-inducible factors, plays a pivotal role in SE. Nevertheless, a chronic state of SE may lead to ineffective erythropoiesis, characterized by the expansion of erythroid progenitor pool, that largely fails to differentiate and give rise to mature red blood cells, further aggravating CRA. In this review, we summarize the current state of knowledge on the emerging roles for stress erythroid progenitors and activated SE pathways in tumor progression, highlighting the urgent need to suppress ineffective erythropoiesis in cancer patients and develop an optimal treatment strategy as well as a personalized approach to CRA management.

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Exposure to hypoxia causes stress erythropoiesis and downregulates immune response genes in spleen of mice

Cited by 21 publications

References 79 publications

Localized Leishmania major infection causes systemic iron deficiency that can be controlled by oral iron supplementation

Localized Leishmania major infection causes systemic iron deficiency that can be controlled by oral iron supplementation

Marked Seasonal Variation in Structure and Function of Gut Microbiota in Forest and Alpine Musk Deer

Targeting Stress Erythropoiesis Pathways in Cancer

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