GDF-15 negatively regulates excess erythropoiesis and its overexpression is involved in erythroid hyperplasia

Ranjbaran, Reza; Abbasi, Mojdeh; Rahimian, Elahe; Dehbidi, Gholamreza Rafiei; Seyyedi, Noorossadat; Zare, Farahnaz; Behzad-Behbahani, Abbas

doi:10.1016/j.yexcr.2020.112346

Cited by 10 publications

(9 citation statements)

References 13 publications

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“…Inhibiting these pathways may be a promising therapeutic strategy to reduce the tumor-promoting activity of nucleated erythroid cells, along with the management of CRA. Furthermore, some of key players in SE, such as SCF/c-kit and GDF15, have been shown to modulate the erythroid cell response to differentiation stimuli and counteract erythroid cell maturation ( Haas et al, 2015 ; Ranjbaran et al, 2020 ). Hence, the inhibition of these pathways, apart from reducing the number of nucleated erythroid cells, may also be beneficial for CRA by promoting erythroid cell maturation in cancer patients.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Targeting Stress Erythropoiesis Pathways in Cancer

et al. 2022

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“…These include SERPINE genes, which are serine protease inhibitors, and GDF15, a well-known marker for ineffective erythropoiesis (Fig. 1C) (Gettins 2002; Ranjbaran et al 2020). Upregulation of representative masters/immune genes in the 3 SF3B1 K700E ES cell lines was validated by qPCR (Fig.…”

Section: Resultsmentioning

confidence: 99%

Chemokine Receptor 1 and its associated immune pathway are downregulated in SF3B1^MT blood and non-blood cancers

Dastpak

Kim

Paraggio

et al. 2022

Preprint

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Mutation of the essential splicing factor SF3B1 is primarily associated with hematological cancers but also occurs in solid tumors. We edited the most common mutation, K700E, into human embryonic stem (ES) cells to determine the effects of this mutation alone in an undifferentiated/non-cancer background. Unexpectedly, >20% of the significantly upregulated genes in the SF3B1K700E ES lines have immune functions. Thus, SF3B1 may have an additional role in proper expression of immune genes in appropriate cell types. In striking contrast, we found that published RNA-seq data from SF3B1 blood (MDS, CLL, AML) and non-blood (BRCA, UVM) cancers exhibited the opposite, downregulation of a multitude of immune pathways with 7 of the pathways shared among all 5 of the SF3B1 cancers. One of these pathways, "leukocyte migration", is the 1st reported pathway shared among all splicing factor cancers, including the 5 SF3B1 cancers and MDS associated with U2AF1, SRSF2 and ZRSR2. Importantly, we identified CCR1, which is in the leukocyte migration pathway as the only shared downregulated gene in the 5 SF3B1 cancers and in U2AF1MT MDS. We conclude that downregulation of CCR1 and its associated immune pathway may play a key role in pathogenesis of these splicing factor cancers and are thus potential therapeutic targets.

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“…It is reported that activated p53 directly enhances the transcriptional activity of GDF-15 gene, resulting in an increase of GDF-15. 85 , 86 …”

Section: Gdf-15 and Signaling Pathwaysmentioning

confidence: 99%

Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease

Tang,

Liu,

Sun

et al. 2024

JIR

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GDF-15 is an essential member of the transforming growth factor-beta superfamily. Its functions mainly involve in tissue injury, inflammation, fibrosis, regulation of appetite and weight, development of tumor, and cardiovascular disease. GDF-15 is involved in various signaling pathways, such as MAPK pathway, PI3K/AKT pathway, STAT3 pathway, RET pathway, and SMAD pathway. In addition, several factors such as p53, ROS, and TNF-α participate the regulation of GDF-15. However, the specific mechanism of these factors regulating GDF-15 is still unclear and more research is needed to explore them. GDF-15 mainly improves the function of kidneys in CKD and plays an important role in the prediction of CKD progression and cardiovascular complications. In addition, the role of GDF-15 in the kidney may be related to the SMAD and MAPK pathways. However, the specific mechanism of these pathways remains unclear. Accordingly, more research on the specific mechanism of GDF-15 affecting kidney disease is needed in the future. In conclusion, GDF-15 may be a therapeutic target for kidney disease.

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GDF-15 negatively regulates excess erythropoiesis and its overexpression is involved in erythroid hyperplasia

Cited by 10 publications

References 13 publications

Targeting Stress Erythropoiesis Pathways in Cancer

Targeting Stress Erythropoiesis Pathways in Cancer

Chemokine Receptor 1 and its associated immune pathway are downregulated in SF3B1^MT blood and non-blood cancers

Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease

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GDF-15 negatively regulates excess erythropoiesis and its overexpression is involved in erythroid hyperplasia

Cited by 10 publications

References 13 publications

Targeting Stress Erythropoiesis Pathways in Cancer

Targeting Stress Erythropoiesis Pathways in Cancer

Chemokine Receptor 1 and its associated immune pathway are downregulated in SF3B1MT blood and non-blood cancers

Role and Mechanism of Growth Differentiation Factor 15 in Chronic Kidney Disease

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Product

Resources

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Chemokine Receptor 1 and its associated immune pathway are downregulated in SF3B1^MT blood and non-blood cancers