Emerging roles of fibroblast growth factor 21 in critical disease

Abstract

In spite of the great progress in the management of critical diseases in recent years, its associated prevalence and mortality of multiple organ failure still remain high. As an endocrine hormone, fibroblast growth factor 21 (FGF21) functions to maintain homeostasis in the whole body. Recent studies have proved that FGF21 has promising potential effects in critical diseases. FGF21 has also been found to have a close relationship with the progression of critical diseases and has a great predictive function for organ failure. The level of FGF21 was elevated in both mouse models and human patients with sepsis or other critical illnesses. Moreover, it is a promising biomarker and has certain therapeutic roles in some critical diseases. We focus on the emerging roles of FGF21 and its potential effects in critical diseases including acute lung injury/acute respiratory distress syndrome (ALI/ARDS), acute myocardial injury (AMI), acute kidney injury (AKI), sepsis, and liver failure in this review. FGF21 has high application value and is worth further studying. Focusing on FGF21 may provide a new perspective for the management of the critical diseases.

Harnessing the Promise of the Cold Stress Response for Acute Brain Injury and Critical Illness in Infants and Children

“…Three had pneumonia with respiratory failure or septic shock, one had toxic shock syndrome, three had severe pulmonary and/or abdominal trauma, and two had abdominal surgical complications with peritonitis. Although data are limited on most components of the CSR in normothermia in critically ill patients, consistent with our findings, a recent review on FGF21 in sepsis, acute lung and kidney injury, myocardial ischemia, and liver failure, supports a robust FGF21 response and suggests that it contributes beneficial effects (65). FGF21 is also a biomarker of mitochondrial disease (mitokine)-particularly in patients with mitochondrial DNA maintenance defects or rearrangement (66), but beyond an association between increased levels and mitochondrial dysfunction, its role is unclear.…”

“…Second, the molecular components that have been co-opted by evolution to be central to CSR have myriad effects on metabolism and cellular function at normothermia (21, 65, 66). These are best described for FGF21 and could be important in critically ill patients.…”

Fibroblast growth factor 21 attenuates ventilator-induced lung injury by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway

“…Numerous clinical and basic studies have shown that FGF21 is involved in metabolic diseases such as diabetes, obesity, and nonalcoholic fatty liver disease [ 10 – 12 ]. Interestingly, FGF21 has been reported to be involved in lipopolysaccharide-induced lung injury [ 13 ], and the emerging roles of FGF21 in acute lung injury/acute respiratory distress syndrome, acute myocardial injury, acute kidney injury, sepsis, and other critical diseases are increasingly noteworthy [ 14 ]. Moreover, several FGF21 analogs, such as Pegbelfermin (Bristol-Myers Squibb), LY2405319 (Eli Lilly), and PF05231023 (Pfizer), have passed Phase I/II trials and were reported to be generally well tolerated and effective in treating obesity or diabetes [ 15 – 17 ].…”

Fibroblast growth factor 21 predicts arteriovenous fistula functional patency loss and mortality in patients undergoing maintenance hemodialysis

“…Fibroblast growth factor 21 (FGF21) is a secreted protein that is involved in a variety of physiological processes, such as metabolic homeostasis, oxidative stress, inflammation, and atherosclerosis [ 7 ]. Elevated levels of FGF21 are associated with coronary artery disease [ 8 ], carotid atherosclerosis [ 9 ], and inflammatory responses (sepsis and ARDS) [ 10 , 11 ]. Our previous studies indicated that FGF21 cooperated with parathyroid hormone to promote the trans-differentiation of endothelial cells into osteoblasts, which promoted vascular calcification (VC) in patients undergoing MHD [ 12 ].…”