GDF-15 and Hepcidin Levels in Nonanemic Patients with Impaired Glucose Tolerance

Yalcin, Mehmet Muhittin; Altınova, Alev Eroğlu; Aktürk, Müjde; Gülbahar, Özlem; Arslan, Emre; Sendogan, Damla Ors; Yetkin, İlhan; Törüner, Füsun Baloş

doi:10.1155/2016/1240843

Cited by 15 publications

(14 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Growth differentiation factor-15 (GDF-15), also called MIC-1 ( 40 ), is a member of the TGF-β superfamily that is up regulated in many cancers, including breast cancer ( 40 , 41 ). GDF-15 has previously been shown to correlate with and potentially regulate hepcidin, although in some contexts GDF-15 may act as an inhibitor rather than an activator of hepcidin (see Discussion and ( 42 – 45 )). We observed that GDF-15 was increased in our breast cancer cell models when compared to non-cancer cells: MCF-7 spheroids had increased GDF-15 compared to MCF-10A spheroids, as did patient tumor spheroids compared to spheroids derived from normal adjacent cells ( Figure 5A and B ).…”

Section: Resultsmentioning

confidence: 93%

“…GDF-15 is induced in response to inflammation, acute injury or malignancy ( 41 , 55 , 56 ). Serum levels of both GDF-15 and hepcidin are increased in patients with breast cancer ( 6 , 41 ) and other malignancies ( 42 , 43 , 57 ). GDF-15 may play multiple roles in cancer; however, studies in breast cancer cells have suggested a role of GDF-15 in enhanced invasion as well as in maintenance of breast cancer stem cells ( 58 , 59 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Contribution of three-dimensional architecture and tumor-associated fibroblasts to hepcidin regulation in breast cancer

et al. 2018

View full text Add to dashboard Cite

Hepcidin is a peptide hormone that negatively regulates iron efflux and plays an important role in controlling the growth of breast tumors. In patients with breast cancer, the combined expression of hepcidin and its membrane target, ferroportin, predict disease outcome. However, mechanisms that control hepcidin expression in breast cancer cells remain largely unknown. Here we use three-dimensional breast cancer spheroids derived from cell lines and breast cancer patients to probe mechanisms of hepcidin regulation in breast cancer. We observe that the extent of hepcidin induction and pathways of its regulation are markedly changed in breast cancer cells grown in three dimensions. In monolayer culture, BMPs, particularly BMP6, regulate hepcidin transcription. When breast cancer cells are grown as spheroids, there is a >10 fold induction in hepcidin transcripts. Microarray analysis combined with knockdown experiments reveal that GDF-15 is the primary mediator of this change. The increase in hepcidin as breast cells develop a three-dimensional architecture increases intracellular iron, as indicated by an increase in the iron storage protein ferritin. Immunohistochemical staining of human breast tumors confirms that both GDF-15 and hepcidin are expressed in breast cancer specimens. Further, levels of GDF-15 are significantly correlated with levels of hepcidin at both the mRNA and protein level in patient samples, consistent with a role for GDF-15 in control of hepcidin in human breast tumors. Inclusion of tumor-associated fibroblasts in breast cancer spheroids further induces hepcidin. This induction is mediated by fibroblast-dependent secretion of IL-6. Breast cancer cells grown as spheroids are uniquely receptive to IL-6-dependent induction of hepcidin by tumor-associated fibroblasts, since IL-6 does not induce hepcidin in cells grown as monolayers. Collectively, our results suggest a new paradigm for tumor-mediated control of iron through the control of hepcidin by tumor architecture and the breast tumor microenvironment.

show abstract

Section: Resultsmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Contribution of three-dimensional architecture and tumor-associated fibroblasts to hepcidin regulation in breast cancer

et al. 2018

View full text Add to dashboard Cite

show abstract

“…[11]. GDF-15, an anti-in ammatory cytokine, is a signi cant regulator of hepcidin and a strong positive correlation has been reported between them in anaemic patients [12,13]. In addition, Erythroblasts secrete GDF-15, which in turn suppresses hepcidin expression and decreases iron stores [14].…”

Section: Introductionmentioning

confidence: 99%

GDF-15 and Hepciden as a therapeutic target for anemia in chronic kidney disease

Farag

mousa

elsayed

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Anaemia is a common presenting feature among patients with chronic kidney disease (CKD) and associated with poor clinical outcomes. We evaluated the diagnostic validity of growth differentiation factor-15 (GDF-15) and hepcidin as it is not clear if they are useful as a biomarkers of anaemia among non-dialysis CKD egyptian patients. Method An analytical cross-sectional study was conducted among non-dialysis CKD patients (n = 60) and apparently healthy controls (n = 28) at Minia University maternity & children Hospital. Serum levels of GDF-15 and hepcidin were determined. Predictive logistic regression models were built and post estimation receiver operator characteristics were determined to evaluate diagnostic validity of hepcidin and GDF-15 for iron deficiency anaemia. Results Hepcidin and GDF-15 are significantly higher in cases than control p value (0.047,<0.0001) respectively. The predictive value of diagnosing anaemia among CKD patients using hepcidin and GDF-15 was 72.0%, 70.0%.There was a weak negative correlation between hepcidin levels and glomerular filtration rate GFR (r-175 =, p = 0.105) in CKD patients, and significant correlation between serum GDF-15 and haemoglobin (r = -0.897, p < 0.0001), ferritin (r = 0.489, P < 0.000), Iron (r=-0.314, P = 0.002), CRP (r = 0.409, P < 0.0001). Conclusion Hepcidin and GDF-15 is a potential biomarker for predicting anaemia connected with inflammation among CKD Egyptian patients.

show abstract

“…Growth Differentiation Factor-15 (GDF-15), an antiinflammatory cytokine, has been suggested as a significant regulator of hepcidin [11]. Oxidative stress and inflammatory conditions can stimulate secretion of GDF-15 by macrophages [12].…”

Section: Introductionmentioning

confidence: 99%

Hepcidin and GDF-15 are potential biomarkers of iron deficiency anaemia in chronic kidney disease patients in South Africa

et al. 2020

View full text Add to dashboard Cite

Background Anaemia is a common presenting feature among patients with chronic kidney disease (CKD) and it is associated with poor clinical outcomes and quality of life. It is not clear if growth differentiation factor-15 (GDF-15) or hepcidin are useful as early markers of iron deficiency anaemia (IDA) among non-dialysis CKD patients. We therefore evaluated the diagnostic validity of GDF-15 and hepcidin as biomarkers of IDA among non-dialysis CKD patients in Johannesburg, South Africa. Method An analytic cross-sectional study was conducted among non-dialysis CKD patients (n = 312) and apparently healthy controls (n = 184) from June to December 2016 at an Academic Hospital, in Johannesburg, South Africa. An interviewer administered proforma was used to obtain the socio-biological and clinical characteristics of the participants. Serum levels of GDF-15 and hepcidin were determined. Predictive logistic regression models were built and post estimation receiver operator characteristics were determined to evaluate diagnostic validity of hepcidin and GDF-15 for absolute and functional iron deficiency anaemia. Results About half (50.6%) of the participants were female while the participants’ mean age was 49.7 ± 15.8 years. The predictive value of diagnosing absolute IDA among CKD patients using GDF-15 was 74.02% (95% CI: 67.62–80.42%) while the predictive value of diagnosing functional IDA among CKD patients using hepcidin was 70.1% (95% CI: 62.79–77.49%).There was a weak negative correlation between hepcidin levels and GFR (r = − 0.19, p = 0.04) in anaemic CKD patients, and between serum GDF-15 and haemoglobin (r = − 0.34, p = 0.001). Serum ferritin (β = 0.00389, P-value< 0.001), was a predictor of log hepcidin. MCHC (β = − 0.0220, P-value 0.005) and CKD stage (β = 0.4761, P-value < 0.001), race (β = 0.3429, P-value = 0.018) were predictors of log GDF-15. Both GDF-15 (adj OR: 1.0003, 95%CI: 1.0001–1.0005, P = 0.017) and hepcidin (adj OR: 1.003, 95%CI: 1.0004–1.0055, P = 0.023) were associated with iron deficiency anaemia after multiple linear regression modelling. Conclusion Serum GDF-15 is a potential biomarker of absolute IDA, while hepcidin levels can predict functional IDA among CKD patients.

show abstract

GDF-15 and Hepcidin Levels in Nonanemic Patients with Impaired Glucose Tolerance

Cited by 15 publications

References 34 publications

Contribution of three-dimensional architecture and tumor-associated fibroblasts to hepcidin regulation in breast cancer

Contribution of three-dimensional architecture and tumor-associated fibroblasts to hepcidin regulation in breast cancer

GDF-15 and Hepciden as a therapeutic target for anemia in chronic kidney disease

Hepcidin and GDF-15 are potential biomarkers of iron deficiency anaemia in chronic kidney disease patients in South Africa

Contact Info

Product

Resources

About