<scp>GDF</scp>15 is a heart‐derived hormone that regulates body growth

Wang, Ting; Liu, Jian; McDonald, Caitlin; Lupino, Katherine; Zhai, Xiandun; Wilkins, Benjamin J.; Hákonarson, Hákon; Pei, Liming

doi:10.15252/emmm.201707604

Cited by 69 publications

(67 citation statements)

References 70 publications

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“…Pediatric heart disease in general induces GDF15 synthesis and secretion by cardiomyocytes. 33 We detected high GDF-15 and normal FGF-21 levels in nine patients with Gaucher disease (seven children, two adults). The elevation did not correlate with the type of Gaucher disease (three patients had type 2, others had type 1 of Gaucher disease).…”

Section: Correlations With Plasma Fgf-21 and Gdf-15mentioning

confidence: 78%

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Plasma FGF‐21 and GDF‐15 are elevated in different inherited metabolic diseases and are not diagnostic for mitochondrial disorders

Tsygankova

Itkis

Крылова

et al. 2019

J of Inher Metab Disea

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Recently, the plasma cytokines FGF‐21 and GDF‐15 were described as cellular metabolic regulators. They share an endocrine function and are highly expressed in the liver under stress and during starvation. Several studies found that these markers have high sensitivity and specificity for the diagnosis of mitochondrial diseases, especially those with prominent muscular involvement. In our study, we aimed to determine whether these markers could help distinguish mitochondrial diseases from other groups of inherited diseases. We measured plasma FGF‐21 and GDF‐15 concentrations in 122 patients with genetically confirmed primary mitochondrial disease and 127 patients with non‐mitochondrial inherited diseases. Although GDF‐15 showed better analytical characteristics (sensitivity = 0.66, specificity = 0.64, area under the curve [AUC] = 0.88) compared to FGF‐21 (sensitivity = 0.51, specificity = 0.76, AUC = 0.78) in the pediatric group of mitochondrial diseases, both markers were also elevated in a variety of non‐mitochondrial diseases, especially those with liver involvement (Gaucher disease, galactosemia, glycogenosis types 1a, 1b, 9), organic acidurias and some leukodystrophies. Thus, the overall positive and negative predictive values were not acceptable for these measurements to be used as diagnostic tests for mitochondrial diseases (FGF‐21 positive predictive value [PPV] = 34%, negative predictive value [NPV] = 73%; GDF‐15 PPV = 47%, NPV = 28%). We suggest that FGF‐21 and GDF‐15 increase in patients with metabolic diseases with metabolic or oxidative stress and inflammation.

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Section: Correlations With Plasma Fgf-21 and Gdf-15mentioning

confidence: 78%

“…Three patients with infantile encephalopathy and hypertrophic cardiomyopathy due to SCO2 and COX10 genes mutations had elevated plasma GDF‐15 with normal FGF‐21. Pediatric heart disease in general induces GDF15 synthesis and secretion by cardiomyocytes …”

Section: Discussionmentioning

confidence: 99%

Plasma FGF‐21 and GDF‐15 are elevated in different inherited metabolic diseases and are not diagnostic for mitochondrial disorders

Tsygankova

Itkis

Крылова

et al. 2019

J of Inher Metab Disea

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“…Adenoviruses were generated as previously described (39,40). Transmission electron microscopy, gene expression, Western blot, cellular oxygen consumption measurement, mitochondrial DNA, and enzyme activity analysis were performed as previously described (18,41). Please see SI Appendix, SI Materials and Methods for detailed description of mouse studies, cell culture, glucose uptake, histological analysis, RNA-Seq, ChIP-Seq, and ChIP-reChIP-Seq experiments.…”

Section: Methodsmentioning

confidence: 99%

Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease

Zhao

Lupino

Qiu

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

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“…In physiological states GDF-15 is secreted by cardiac myocytes and it regulated growth and proliferation of tissues located in heart and vessels [10]. Therefore, GDF-15 is realized by cardiac cells due to fluid retention and pressure overload, as well as it produced in resulting in inflammation and cell-to-cell cooperation [11].…”

Section: Introductionmentioning

confidence: 99%

Growth-Differentiation Factor-15 as Additional Prognostic Biomarkers in Heart Failure

Berezin¹

2017

Metabolomics

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Heart Failure (HF) remains to be a leading factor of cardiovascular morbidity and mortality. Although risk stratification of HF is promising prediction care, there are several controversies regarding choosing more optimal combinations of biomarkers and method (single versus serial measurements) of biomarker use in routine clinical practice. Growth differentiation factor-15 (GDF-15) is considered a biomarker associated with cardiac/vascular remodeling, oxidative stress, fibrosis and inflammation that were proposed to stratify HF patients at risk of death. It has been suggested that GDF-15 adding to natriuretic peptides or other conventional biomarkers (soluble ST2, cardiac troponins and galectin-3) might improve discriminative value of entire predictive models. The short communication is depicted the discussion about the perspectives of clinical use of GDF-15 in risk stratification of HF.

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GDF15 is a heart‐derived hormone that regulates body growth

Cited by 69 publications

References 70 publications

Plasma FGF‐21 and GDF‐15 are elevated in different inherited metabolic diseases and are not diagnostic for mitochondrial disorders

Plasma FGF‐21 and GDF‐15 are elevated in different inherited metabolic diseases and are not diagnostic for mitochondrial disorders

Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease

Growth-Differentiation Factor-15 as Additional Prognostic Biomarkers in Heart Failure

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