GDF3

What is GDF3 protein?

GDF3 gene (growth differentiation factor 3) is a protein coding gene which situated on the short arm of chromosome 12 at locus 12p13. This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein plays a role ocular and skeletal development. The GDF3 protein is consisted of 364 amino acids and GDF3 molecular weight is approximately 41.4 kDa.

What is the function of GDF3 protein?

The GDF3 protein is a protein belonging to the transforming growth factor β (TGF-β) superfamily. GDF3 plays an important role in early embryonic development, bone and retinal development. Including: involved in the regulation of cell fate and cell pluripotency, involved in the regulation of bone and cartilage growth and maturation. During embryogenesis, GDF3 influences the formation of provisceral endoderm and mesoderm by controlling the establishment of pre - and post-identity. As a member of TGF-β superfamily, GDF3 activates SMAD family transcription factors by binding to corresponding receptors, thereby regulating gene expression. GDF3 is involved in regulating the homeostasis and energy balance of adipose tissue under nutrient overload.

GDF3 Related Signaling Pathway

By binding to TGF-β receptor, GDF3 activates SAMad-dependent signaling pathway, affecting cell proliferation, differentiation and apoptosis. In some cases, GDF3 can inhibit BMP signaling pathways and affect cell fate decisions. GDF3 is specifically expressed in embryonic stem cells and is involved in the regulation of self-renewal and pluripotency maintenance of stem cells. Studies have shown that GDF3 at high doses activates the Nodal signaling pathway, an important signaling pathway associated with early embryonic pattern formation. GDF3 may influence cell behavior through a non-mad dependent pathway, such as activating other signaling pathways such as MAPK.

GDF3 Related Diseases

Klippel-Feil syndrome is a disease characterized by abnormal fusion of the vertebrae in the neck and affects many parts of the body. At least four mutations in the GDF3 gene have been found to cause this syndrome, and these mutations may reduce levels of functional proteins. The GDF3 protein is also involved in the development of the eye, particularly the retina. Mutations in the GDF3 gene are associated with certain eye diseases, such as retinal dysplasia. GDF3 may play a role in regulating the host's response to infection, for example in a model of sepsis, where GDF3 administration improves survival in mice. In addition, it is associated with cardiomyopathy and some tumors.

Fig1. Scheme depicting that administration of GDF3 into septic mice improves survival via enhancing macrophage phagocytosis. (Peng Wang, 2021)

Bioapplications of GDF3

GDF3 has been identified as a biomarker of adverse fibrosis remodeling after myocardial infarction and is helpful in understanding the process of cardiac fibrosis scar formation after myocardial infarction. As an inhibitor of the BMP (bone morphogenetic proteins) family, the regulatory effects of GDF3 have potential applications in drug development, especially in the treatment of diseases associated with BMP signaling pathways. Due to GDF3's role in bone and cartilage development, it may be used in tissue engineering and regenerative medicine to promote tissue repair and regeneration. The role of GDF3 in early embryonic development makes it an important molecule to study the mechanism of embryonic development, which helps to reveal the molecular mechanism of embryo formation and organ development.