Regulation and Potential Biological Role of Fibroblast Growth Factor 21 in Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is an incurable progressive disease with the progressive impairment of kidney function, which can accelerate the progression of cardiovascular disease, increase the risk of infection, and lead to related complications such as anemia and bone disease. CKD is to a great extent preventable and treatable, and it is particularly important to improve the early diagnosis, strengthen the research underlying the mechanism of disease occurrence and development, and innovate new intervention measures. Fibroblast growth factor 21 (FGF21) belongs to one of members of endocrine FGF subfamily with evolutionarily conserved functions and performs a vital role in the regulation of energy balance and adipose metabolism. FGF21 needs to rely on β-Klotho protein to specifically bind to FGF receptor (FGFR), which activates the FGF21 signaling exerting the biological function. FGF21 is deemed as an important regulatory factor extensively modulating many cellular functions under physiologic and pathologic conditions. Although the metabolic effect of FGF21 has been extensively studied, its potential biological role in the kidney has not been generally investigated. In this review, we summarize the biological characteristics, regulation and biological function of FGF21 based on the current studies, and briefly discuss the potential relationship with chronic kidney disease.

New developments in the biology of fibroblast growth factors

“…FGF21 exerts various physiological and pharmacological effects on glucose and lipid metabolism through its endocrine actions in both the CNS and peripheral tissues. In humans, FGF21 is thought to be involved in metabolic diseases including nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), CKD, and cardiovascular disorders (Geng et al, 2020; Li, 2019; Tucker et al, 2020; X. Zhou, Zhang, & Wang, 2021).…”

Folic acid‐induced animal model of kidney disease

“…While it is well established that oxidative damage reflected by enhanced lipid peroxidation and deceased levels of glutathione and antioxidant capacity is the culminating event leading to cell death of tubular epithelial cells including apoptosis, necrosis, and ferroptosis, the upstream signaling processes are multifactorial. These include downregulation of klotho, 177,190 and increased expression of FGF21 and FGF23, 183,184,191 the latter of which is likely regulated by interleukin-6. 185 FGF21 also relies on beta-klotho protein to bind fibroblast growth factor receptor to exert its biological function in the kidney.…”

“…185 FGF21 also relies on beta-klotho protein to bind fibroblast growth factor receptor to exert its biological function in the kidney. 191 In addition, among the genes affected by FA-induced kidney injury, c-myc and c-fos, involved in initiating cell cycle events, are believed to be the primary response genes. 192 Nonetheless, the exact roles of these response genes in FA-induced kidney injury remains to be comprehensively evaluated.…”

Bruxism and Botulinum Injection: Challenges and Insights

“…[40]; -Chronic headaches (when botulinum toxin A injections were used in patients undergoing cosmetic treatment with an associated headache, improvement in chronic headache was observed [41,42]; -Hyperhidrosis (usually affects armpits, hands, and feet) [43,44]; -Trigeminal neuralgia. There are several case reports and studies demonstrating its effectiveness to reduce the symptoms of this disorder [45], such as numbness, tingling, and scratching sensation in the affected areas [46,47]; -Masseter hypertrophy (Figure 3). Usually, patients with a history of bruxism are affected, and the appearance of their faces may change due to the increased size of the muscle.…”