GDF15 as a key disease target and biomarker: linking chronic lung diseases and ageing

Abstract

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta superfamily, is expressed in several human organs. In particular, it is highly expressed in the placenta, prostate, and liver. The expression of GDF15 increases under cellular stress and pathological conditions. Although numerous transcription factors directly up-regulate the expression of GDF15, the receptors and downstream mediators of GDF15 signal transduction in most tissues have not yet been determined. Glial cell-derived neurotrophic factor family receptor α-like protein was recently identified as a specific receptor that plays a mediating role in anorexia. However, the specific receptors of GDF15 in other tissues and organs remain unclear. As a marker of cell stress, GDF15 appears to exert different effects under different pathological conditions. Cell senescence may be an important pathogenetic process and could be used to assess the progression of various lung diseases, including COVID-19. As a key member of the senescence-associated secretory phenotype protein repertoire, GDF15 seems to be associated with mitochondrial dysfunction, although the specific molecular mechanism linking GDF15 expression with ageing remains to be elucidated. Here, we focus on research progress linking GDF15 expression with the pathogenesis of various chronic lung diseases, including neonatal bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and pulmonary hypertension, suggesting that GDF15 may be a key biomarker for diagnosis and prognosis. Thus, in this review, we aimed to provide new insights into the molecular biological mechanism and emerging clinical data associated with GDF15 in lung-related diseases, while highlighting promising research and clinical prospects.

Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) and Growth Differentiation Factor-15 (GDF-15) Levels Are Significantly Associated with Endothelial Injury Indices in Adult Allogeneic Hematopoietic Cell Transplantation Recipients

“…The exact function of GDF-15 is still not completely understood; however, it appears to be involved in several cellular processes such as apoptosis, cell repair, and cell development and has a role in the regulation of inflammatory pathways. GDF15 serves as a broad-spectrum biomarker for several diseases, such as cardiovascular, pulmonary, and renal as well as for malignancies [ 15 ]. It has been shown that GDF-15 can modify vascular relaxation and contraction responses in an endothelial-dependent manner that involves the nitric oxide pathway [ 56 ].…”

“…Moreover, it has been recently shown that EASIX can serve as a predictive marker for both complement activation and overall survival in patients with GvHD and HSCT-TMA [ 12 ]. soluble urokinase plasminogen activator receptor (suPAR) and growth differentiation factor-15 (GDF-15) have been determined as endothelial injury indices in various clinical settings in both hematological and non-hematological diseases [ 13 , 14 , 15 , 16 ].…”

Epigenetic scores indicate differences in the proteome of preterm infants

“…As well as having specific immunoregulatory roles, in the neonatal setting or relevant animal models, these proteins are associated with several comorbidities and developmental consequences of preterm birth. These include lung development and disease such as BPD [55][56][57][58][59][60][61][62][63][64][65][66][67], in utero and postnatal growth failure [68][69][70][71], HCA [7,72,73], patent ductus arteriosus [74][75][76][77], retinopathy of prematurity [78][79][80][81][82], NEC [83][84][85], hyperglycaemia [86], sepsis [85,[87][88][89][90], brain injury [32,[91][92][93][94], and neurodevelopmental outcomes [95][96][97][98]…”

p53-induced GDF-15 expression promotes a pro-regenerative response in human chondrocytes upon cartilage injury

“…Despite its bad reputation as all-cause mortality marker, increased GDF-15 expression has also been discussed as a survival response [11]. Accordingly, GDF-15 is produced by various cell types during acute tissue injury and was described as prominent senescence-associated secretory phenotype (SASP) factor in senescent cells [12]. Although transient senescence is considered as beneficial in terms of tissue remodelling and repair, chronic accumulation of senescent cells in cartilage or other tissues contributes to progressive degeneration and dysfunction due to the excessive secretion of catabolic and pro-inflammatory SASP factors [13, 14].…”