Growth differentiation factor 15 (GDF15) is expressed in normal conditions but is overly expressed when cells are under stress. It has multiple roles in different diseases and has been used as a biomarker for many conditions. It also can predict mortality. However, researchers are still working on understanding all of the mechanisms by which GDF15 works to exert pulmonary symptoms. This article discusses the different effects this factor can have on various lung conditions, as well as how it impacts cellular senescence, or the stopping of cell division, as this is something that plays a major role in lung diseases.
First it is important to clarify that GDF15 also goes by another name- MIC-1. This is because it inhibits the production of TNF-a, located in the macrophages.
Researchers have found many factors that increase the expression of GDF15. The factor has two different P53 binding sites. P53 works to induce the factor, and the factor then modulates p53 growth suppression within tumor cells. Other findings include-
- EGR-1 and SP1 have the same binding site on GDF15
- PPAR-y and ATF-3 can both induce the expression of GDF15
- Anoxia can induce the expression independent of p53
- NSAIDS can induce expression independent of 53
- GFRAL has a high affinity to the factor
- RET is necessary for the signaling of GDF15
- When GDF15 binds to GFRAL-RET, signaling influencing AKT, ERK, and PLC-y erupts
GDF15 plays a role in both neonatal and pediatric lung diseases such as bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis, and cell senescence. However, researchers have found that different pathways are initiated depending on the condition and area of the body affected. Even within lung diseases, its presentation differs.
Ultimately, these researchers have determined that GDF15 contributes to many lung diseases. Associated lung diseases all are affected by senescence. The protein is also associated with-
- Activation of senescence pathways
Researchers are still investigating-
- The pathways through which the factor acts
- The receptors that the protein has an effect within
- Whether or not inflammatory cells increase the levels of the protein within the lung
- If epigenetic mechanisms are a factor in expression
- If effects on organs are mediated through the expression of the protein
- If expression is adaptive or protective or harmful for each condition
- The transcription factors present
- In what cases it would be a useful biomarker
- In what cases it would be a useful therapeutic target
It is essential for researchers to continue to examine this protein in lung diseases as it is clear its expression and role varies greatly across indications.
You can read more about the role of this factor here.