GDF15

Case Study 1: Jyoti Asundi, 2024

Characterize Growth Differentiation Factor 15 (GDF15) as a secreted biomarker of the integrated stress response (ISR) within the central nervous system (CNS). The researchers determined GDF15 levels utilizing in vitro and in vivo neuronal systems wherein the ISR was activated. Primarily, they used the murine model of vanishing white matter disease (VWMD), a neurological disease driven by persistent ISR in the CNS, to establish a link between levels of GDF15 in the cerebrospinal fluid (CSF) and ISR gene expression signature in the CNS. GDF15 was also determined in the CSF of VWM patients. GDF15 expression was increased concomitant to ISR activation in stress-induced primary astrocytes as well as in retinal ganglion cells following optic nerve crush, while treatment with 2Bact, a specific eIF2B activator, suppressed both the ISR and GDF15. In the VWMD model, CSF GDF15 levels corresponded with the magnitude of the ISR and were reduced by 2BAct. In VWM patients, mean CSF GDF15 was elevated >20-fold as compared to healthy controls, whereas plasma GDF15 was undifferentiated.

Fig1. Secretion of GDF15 protein are elevated in primary rat astrocytes.

Fig2. GDF15 expression levels are differentially elevated in cerebrospinal fluid (CSF).

Case Study 2: Lukas Lösch, 2023

Periodontal ligament fibroblasts (PdLFs) exert important functions in oral tissue and bone remodeling following mechanical forces, which are specifically applied during orthodontic tooth movement (OTM). Located between the teeth and the alveolar bone, mechanical stress activates the mechanomodulatory functions of PdLFs including regulating local inflammation and activating further bone-remodeling cells. Previous studies suggested growth differentiation factor 15 (GDF15) as an important pro-inflammatory regulator during the PdLF mechanoresponse. GDF15 exerts its effects through both intracrine signaling and receptor binding, possibly even in an autocrine manner. The extent to which PdLFs are susceptible to extracellular GDF15 has not yet been investigated. Thus, this study aims to examine the influence of GDF15 exposure on the cellular properties of PdLFs and their mechanoresponse, which seems particularly relevant regarding disease- and aging-associated elevated GDF15 serum levels. Therefore, in addition to investigating potential GDF15 receptors, they analyzed its impact on the proliferation, survival, senescence, and differentiation of human PdLFs, demonstrating a pro-osteogenic effect upon long-term stimulation.

Fig3. Co-immunoprecipitation with ALK1, ALK2, and ALK5-specific antibodies (ALK1/2/5-Ab) to detect GDF15 binding by those receptors in hPdLFs stimulated with 5 ng/mL recombinant human GDF15.

Fig4. TRAP-positive THP1 cells indicating the differentiation into osteoclasts, when stimulated with the medium supernatant of 36-day rhGDF15-stimulated hPdLFs additionally stressed with CF.

Fig1. A schematic representation of the Macrophage inhibitory cytokine-1 (MIC-1) signaling pathway in cell proliferation. (Sakthivel Muniyan, 2022)

Fig2. GDF15 signaling in cancer. (Jawed Akhtar Siddiqui, 2022)

GDF15 involved in several pathways and played different roles in them. We selected most pathways GDF15 participated on our site, such as Direct p53 effectors, which may be useful for your reference. Also, other proteins which involved in the same pathway with GDF15 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

GDF15 has several biochemical functions, for example, cytokine activity, growth factor activity, transforming growth factor beta receptor binding. Some of the functions are cooperated with other proteins, some of the functions could acted by GDF15 itself. We selected most functions GDF15 had, and list some proteins which have the same functions with GDF15. You can find most of the proteins on our site.

GDF15 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with GDF15 here. Most of them are supplied by our site. Hope this information will be useful for your research of GDF15.

MDFI; MAPK14; Trip11; ssrna_a; STAT5A; Smn1; Cdc37; MRPL50; NUPL1; SETD4; SAE1