Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy

Andersson‐Hall, Ulrika; Svedin, Pernilla; Mallard, Carina; Blennow, Kaj; Zetterberg, Henrik; Holmäng, Agneta

doi:10.1101/2021.03.10.434730

Cited by 5 publications

(1 citation statement)

References 44 publications

(58 reference statements)

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“…In addition, the production of GDF15 by adipocytes is also induced by oxidative stress, a well-known to cause preeclampsia 19 . In pregnant women, the circulating level of GDF-15 is shown to significantly increase to approximately a 15-fold of the non-pregnant women 20 . Moreover, variations of the circulating levels of GDF-15 have been noticed in women with miscarriage 21 22 and gestational diabetes mellitus 23 .…”

Section: Introductionmentioning

confidence: 95%

Circulating Growth Differentiation Factor 15 and Preeclampsia: A Meta-Analysis

Wang

Yang

2022

Horm Metab Res

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Growth differentiation factor 15 (GDF-15) has been suggested as a potential biomarker of preeclampsia. However, previous studies evaluating circulating GDF-15 in women with preeclampsia showed inconsistent results. A meta-analysis was performed accordingly in this study. Observational studies comparing circulating GDF-15 between women with preeclampsia normal pregnancy were identified by search of electronic databases including PubMed, Embase, Web of Science, Wanfang, and CNKI. The Newcastle-Ottawa Scale (NOS) was used for assessing the quality of the studies. A randomized-effect model incorporating the possible between-study heterogeneity was used to pool the results. Eleven observational studies including 498 women with preeclampsia and 2349 women with normal pregnancy contributed to the meta-analysis. Results showed that compared to controls of women with normal pregnancy at least matched for gestational ages, women with preeclampsia had significantly higher circulating GDF-15 at the diagnosis [standard mean difference (SMD): 0.66, 95% confidence interval (CI): 0.16 to 1.17, p=0.01, I2=93%]. Subgroup analysis showed consistent results in women with preterm and term preeclampsia in Asian and non-Asian women and in studies with different quality scores, which were not statistically significant between subgroups (p for subgroup difference>0.05). Moreover, a higher level of GDF-15 was also found before the diagnosis in women who subsequently developed preeclampsia than those who did not (SMD: 1.32, 95% CI: 0.45 to 2.18, p=0.003, I2=89%). In conclusion, a higher circulating GDF-15 is observed in women with preeclampsia even before the diagnosis of the disease.

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Section: Introductionmentioning

confidence: 95%

Circulating Growth Differentiation Factor 15 and Preeclampsia: A Meta-Analysis

Wang

Yang

2022

Horm Metab Res

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GDF15 Is an Eribulin Response Biomarker also Required for Survival of DTP Breast Cancer Cells

Bellio¹,

Emperador²,

Castellano‐Escuder³

et al. 2022

Cancers

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Drug tolerant persister (DTP) cells enter into a reversible slow-cycling state after drug treatment. We performed proteomic characterization of the breast cancer (BC) DTP cell secretome after eribulin treatment. We showed that the growth differentiation factor 15 (GDF15) is a protein significantly over-secreted upon eribulin treatment. The biomarker potential of GDF15 was confirmed in 3D-cell culture models using BC cells lines and PDXs, as well as in a TNBC in vivo model. We also found that GDF15 is required for survival of DTP cells. Direct participation of GDF15 and its receptor GFRAL in eribulin-induction of DTPs was established by the enhanced cell killing of DTPs by eribulin seen under GDF15 and GFRAL loss of function assays. Finally, we showed that combination therapy of eribulin plus an anti-GDF15 antibody kills BC-DTP cells. Our results suggest that targeting GDF15 may help eradicate DTP cells and block the onset of acquired resistance.

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The Role of GDF15 as a Myomitokine

Johann

Kleinert

Schimrigk

2021

Cells

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Growth differentiation factor 15 (GDF15) is a cytokine best known for affecting systemic energy metabolism through its anorectic action. GDF15 expression and secretion from various organs and tissues is induced in different physiological and pathophysiological states, often linked to mitochondrial stress, leading to highly variable circulating GDF15 levels. In skeletal muscle and the heart, the basal expression of GDF15 is very low compared to other organs, but GDF15 expression and secretion can be induced in various stress conditions, such as intense exercise and acute myocardial infarction, respectively. GDF15 is thus considered as a myokine and cardiokine. GFRAL, the exclusive receptor for GDF15, is expressed in hindbrain neurons and activation of the GDF15–GFRAL pathway is linked to an increased sympathetic outflow and possibly an activation of the hypothalamic-pituitary-adrenal (HPA) stress axis. There is also evidence for peripheral, direct effects of GDF15 on adipose tissue lipolysis and possible autocrine cardiac effects. Metabolic and behavioral outcomes of GDF15 signaling can be beneficial or detrimental, likely depending on the magnitude and duration of the GDF15 signal. This is especially apparent for GDF15 production in muscle, which can be induced both by exercise and by muscle disease states such as sarcopenia and mitochondrial myopathy.

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Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy

Cited by 5 publications

References 44 publications

Circulating Growth Differentiation Factor 15 and Preeclampsia: A Meta-Analysis

Circulating Growth Differentiation Factor 15 and Preeclampsia: A Meta-Analysis

GDF15 Is an Eribulin Response Biomarker also Required for Survival of DTP Breast Cancer Cells

The Role of GDF15 as a Myomitokine

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