The Clinical Value of GDF15 and Its Prospective Mechanism in Sepsis

Abstract

Growth differentiation factor 15 (GDF15) is involved in the occurrence and development of many diseases, and there are few studies on its relationship with sepsis. This article aims to explore the clinical value of GDF15 in sepsis and to preliminarily explore its prospective regulatory effect on macrophage inflammation and its functions. We recruited 320 subjects (132 cases in sepsis group, 93 cases in nonsepsis group, and 95 cases in control group), then detected the serum GDF15 levels and laboratory indicators, and further investigated the correlation between GDF15 and laboratory indicators, and also analyzed the clinical value of GDF15 in sepsis diagnosis, severity assessment, and prognosis. In vitro, we used LPS to stimulate THP-1 and RAW264.7 cells to establish the inflammatory model, and detected the expression of GDF15 in the culture medium and cells under the inflammatory state. After that, we added GDF15 recombinant protein (rGDF15) pretreatment to explore its prospective regulatory effect on macrophage inflammation and its functions. The results showed that the serum GDF15 levels were significantly increased in the sepsis group, which was correlated with laboratory indexes of organ damage, coagulation indexes, inflammatory factors, and SOFA score. GDF15 also has a high AUC in the diagnosis of sepsis, which can be further improved by combining with other indicators. The dynamic monitoring of GDF15 levels can play an important role in the judgment and prognosis of sepsis. In the inflammatory state, the expression of intracellular and extracellular GDF15 increased. GDF15 can reduce the levels of cytokines, inhibit M1 polarization induced by LPS, and promote M2 polarization. Moreover, GDF15 also enhances the phagocytosis and bactericidal function of macrophages. Finally, we observed a decreased level of the phosphorylation of JAK1/STAT3 signaling pathway and the nuclear translocation of NF-κB p65 with the pretreatment of rGDF15. In summary, our study found that GDF15 has good clinical application value in sepsis and plays a protective role in the development of sepsis by regulating the functions of macrophages and inhibiting the activation of JAK1/STAT3 pathway and nuclear translocation of NF-κB p65.

Growth Differentiation Factor 15 Regulates Oxidative Stress-Dependent Ferroptosis Post Spinal Cord Injury by Stabilizing the p62-Keap1-Nrf2 Signaling Pathway

“…The short hairpin (sh) RNAs targeting GDF15 and p62 (BIOG, Changzhou, China) for knockdown were loaded in plasmids, respectively, and transfected into primary neurons by RFect Plasmid Transfection Reagent (BIOG) for 24 h. Recombinant GDF15 (rGDF5; ab202199, Abcam, Cambridge, MA, United States) was used to provide exogenetic expression of GDF15 in vitro ( Li H. et al, 2021 ). The shRNA-GDF15 loaded in adeno-associated virus (AAV) vectors was obtained from Genechem CO., LTD (Shanghai, China).…”

Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-on-chronic liver failure

“…GDF15 and FGF21 Levels in tissue homogenates were examined to reveal mitochondrial dysfunction. GDF15 and FGF21 are circulating markers for mitochondrial disorders and are widely used in diagnosis of mitochondrial diseases[ 7 - 9 ] and other serious diseases, such as liver failure[ 4 , 10 , 11 ], heart failure[ 12 , 13 ], and sepsis[ 14 , 15 ]. Their expression levels positively correlated with disease severity.…”

GDF15 Improves Lipopolysaccharide-Induced Myocardial Dysfunction By Inhibiting Cardiomyocyte Ferroptosis Via The SOCS1/GPX4 Signaling Pathway Regulation

“…Our results showed that serum and myocardial GDF15 levels are drastically increased in sepsis. Li et al found that GDF15 is clinically valuable in treating sepsis and plays a protective role against sepsis development [13]. Additionally, GDF15 can predict LVEF changes in cardiovascular diseases [34].…”