GDF15, an update of the physiological and pathological roles it plays: a review
- PDF / 1,289,252 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 16 Downloads / 220 Views
INVITED REVIEW
GDF15, an update of the physiological and pathological roles it plays: a review Artin Assadi 1,2
&
Azadeh Zahabi 3
&
Robert A. Hart 4
Received: 29 March 2020 / Revised: 6 August 2020 / Accepted: 2 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Growth differentiation factor 15 (GDF15) is a peptide hormone, and a divergent member of the transforming growth factor beta (TGFβ) superfamily. In normal physiology, GDF15 is expressed in multiple tissues at a low concentration. GDF15 is overexpressed during and following many pathological conditions such as tissue injury and inflammation in order to play a protective role. However, GDF15 appears to promote tumour growth in the later stages of malignant cancer. The recently identified endogenous receptor for GDF15, GDNF family receptor a-like (GFRAL), has allowed elucidation of a physiological pathway in which GDF15 regulates energy homeostasis and body weight, primarily via appetite suppression. The anorectic effect of GDF15 provides some therapeutic potential in management of cancer-related anorexia/cachexia and obesity. Despite the identification of GFRAL as a GDF15 receptor, there appears to be other signalling mechanisms utilized by GDF15 that further increase the possibility of development of therapeutic treatments, should these pathways be fully characterized. In this review, GDF15 function in both physiological and pathological conditions in various tissues will be discussed. Keywords GDF15 . TGFβ . GFRAL . Energy homeostasis . Cancer
Introduction In 1997, Bootcov and colleagues cloned growth differentiation factor 15 (GDF15) from human monocytoid cell line U937 [8]. At that time, they discovered GDF15 as an autocrine protein able to modulate macrophages activated by lipopolysaccharide (LPS), suppressing TNF-α production. Therefore, GDF15 was initially named macrophage inhibitory cytokine-1 (MIC-1) [8]. Due to a broad spectrum of biological functions in both physiological and pathological processes, GDF15 has been known by several other names [62]. It has been referred to as nonsteroidal anti-inflammatory drug–
activated gene-1 (NAG-1) [4], placental transformation growth factor-β (PTGFB) [45], prostate-derived factor (PDF) [72] and placental bone morphogenetic protein (PLAB) [33]. GDF15 belongs to the transforming growth factor beta (TGFβ) superfamily [39], and has roles as a hormone [41], stress-induced cytokine or stress-sensitive circulating factor [60]. In this review, the normal physiological and pathological roles of GDF15 will be summarized for muscle, brain, heart and kidney tissues, as well as changes in GDF15 function in ageing, cancer and metabolism.
Transforming growth factor beta superfamily * Robert A. Hart [email protected] 1
Department of Pilot Biotechnology, Pasteur Institute, Tehran, Iran
2
Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3
Department of Oncology, Hematology, Immunology, Rheumatology, and Pulmonology, University H
Data Loading...
