FGF-23 recombinant protein: the core regulatory factor of mineral metabolism disorders in chronic kidney disease

Author: Senior Product Manager of UA Views：6

This article focuses on the molecular characteristics and biological functions of fibroblast growth factor 23 (FGF-23), systematically elaborating its core regulatory role as a phosphaturic hormone in mineral metabolism disorders in chronic kidney disease, analyzing the interaction mechanisms between FGF-23 and calcium and phosphorus metabolism as well as the clinical significance of the signaling axis formed with Klotho in the progression of CKD, and exploring the application prospects of FGF-23 as a new target for the diagnosis and treatment of CKD.

Recent Advances
Product Information

Recent Advances

FGF-23 Recombinant Protein: A Core Regulatory Factor in Mineral Metabolism Disorders of Chronic Kidney Disease

Brief Introduction: This article focuses on the molecular characteristics and biological functions of fibroblast growth factor 23 (FGF-23), systematically elaborating its core regulatory role as a phosphaturic hormone in mineral metabolism disorders of chronic kidney disease, analyzing the interaction mechanisms between FGF-23 and calcium and phosphorus metabolism as well as the clinical significance of the signaling axis it forms with Klotho in the progression of CKD, and discussing the application prospects of FGF-23 as a new target for CKD diagnosis and treatment.

I. Molecular Characteristics and Expression Regulation of FGF-23.

Fibroblast growth factor 23 (FGF-23) is an endocrine-type signaling protein secreted by osteocytes and osteoblasts, belonging to the FGF-19 subfamily. The mature FGF-23 protein consists of 227 amino acids, and its structure can be divided into three functional regions: the N-terminal fibroblast growth factor receptor binding domain, the C-terminal α-Klotho binding domain, and the proteolytic cleavage site located between the two. FGF-23 is mainly derived from osteoblasts and osteoclasts, and is regulated by serum phosphorus, active vitamin D, parathyroid hormone, and Klotho, playing an important role in maintaining bone metabolic balance. Under physiological conditions, FGF-23 exerts its core function as a phosphaturic hormone by binding to the FGFR1/c-Klotho receptor complex on the surface of renal proximal tubular cells.

II. Interaction Between FGF-23 and Calcium Metabolism in CKD.

Patients with chronic kidney disease are prone to bone and mineral metabolism abnormalities, which activate fibroblast growth factor 23. FGF-23 is not only involved in the pathological process of CKD-MBD and affects calcium and phosphorus metabolism, but also forms the Klotho/FGF-23 signaling axis with Klotho to participate in the progression of CKD. Previous studies have found that vitamin D and its metabolites affect FGF-23 levels. In CKD patients, FGF-23 levels continuously increase, inhibiting 1,25(OH)2D3, thereby leading to secondary hyperparathyroidism; high levels of PTH can further elevate FGF-23 levels, thus forming a vicious cycle.

The research results published by Berg et al. in 2017 showed that vitamin D2 supplementation can increase 24,25(OH)2D3, reduce 25-hydroxyvitamin D3 by inducing 24-hydroxylase, and increase the ratio of vitamin D metabolites. The study also found that the elevated ratio of vitamin D products did not affect PTH and FGF-23 levels. This latest research result indicates that controlling FGF-23 levels in CKD patients through the vitamin D pathway still awaits new breakthroughs. Another study found that direct intravenous infusion of calcium agents in patients can induce short-term elevation of serum calcium concentration, but did not affect FGF-23 levels. Although a secondary analysis of 2,900 patients in the EVOLVE study showed that reducing serum calcium or PTH can simultaneously reduce FGF-23 levels. However, for CKD/ESRD patients, calcium binders cannot synchronously reduce FGF-23, and may instead elevate FGF-23 levels. To this day, whether reducing FGF-23 levels in CKD and ESRD patients has clinical significance remains the greatest confusion in this field.

III. Association Between FGF-23 and Phosphorus Metabolism in CKD.

Clinical studies have found that both FGF-23 and serum phosphorus levels are elevated in CKD patients, and the upregulation of FGF-23 and serum phosphorus levels is positively correlated with the morbidity and mortality of CKD. Dietary and intravenous phosphate infusion can lead to phosphorus accumulation, triggering PTH and indirectly causing delayed elevation of FGF-23 levels; in contrast, high intake of plant protein can downregulate FGF-23 levels.

A 2017 study by Liabeuf et al. found that in CKD patients with normal serum phosphorus, the urinary phosphate/creatinine ratio decreased, while cFGF-23 and serum phosphorus levels did not change. In CKD patients with hyperphosphatemia, cFGF-23 did not significantly decrease with changes in calcium acetate levels. However, after ESRD patients used phosphate-lowering drugs such as sevelamer, FGF-23 levels decreased accordingly. It is currently believed that calcium and phosphorus, ions, inflammation, and many other factors may all participate in the interaction between FGF-23 and serum phosphorus. These complex regulatory relationships indicate that FGF-23 occupies a core regulatory position in CKD mineral metabolism disorders, but its causal relationship with serum phosphorus still requires further research.

IV. Klotho/FGF-23 Signaling Axis and CKD Progression.

FGF-23 relies on the Klotho signaling pathway to activate FGFRs and exert biological effects, and excessively high FGF-23 also relies on Klotho to initiate pathophysiological effects. In the early stages of CKD, Klotho decreases in blood and urine, accompanied by elevated FGF-23 levels in the blood. This change in FGF-23 levels is regarded as an early biological marker of CKD. Studies have shown that decreased Klotho levels are closely associated with CKD progression, vascular calcification, cardiac fibrosis, and cardiac hypertrophy.

At the 2018 ASN conference, Mark Danese et al. reported that the results of the EVOLVE study confirmed that Klotho/FGF-23 participates in the development of cardiovascular disease and is a predictor of cardiovascular event onset and death in CKD patients and the general population. Therefore, preventing the decrease of Klotho, increasing endogenous Klotho production, and supplementing exogenous Klotho can reduce renal fibrosis, delay CKD progression, improve CKD-MBD conditions, and reduce the risk of cardiomyopathy and vascular calcification, with significant clinical importance. Related research in this area is being carried out in depth, and the potential of the Klotho/FGF-23 signaling axis as a therapeutic target for CKD is being gradually recognized.

V. Application Prospects of FGF-23 as a New Target for CKD Diagnosis and Treatment.

A large amount of clinical data shows that FGF-23 concentration gradually increases with the progression of CKD, and CKD-MBD mostly occurs after the elevation of FGF-23. It is currently believed that FGF-23 is the earliest appearing detection indicator of CKD-MBD. Gutierrez et al. found that FGF-23 levels can predict mortality in CKD patients. Evaluating CKD conditions through FGF-23 levels is gradually being accepted.

From a therapeutic perspective, using antibodies to deplete FGF-23 may increase the incidence of vascular calcification and hyperphosphatemia. Therefore, for CKD patients, while reducing FGF-23 levels through intervention measures, it is still necessary to use ion-binding drugs such as sevelamer to control calcium and phosphorus metabolism. Looking ahead, a comprehensive diagnosis and treatment strategy for CKD targeting FGF-23 is worth anticipating. In FGF-23-related basic research and drug development, high-quality recombinant FGF-23 protein is a core tool for analyzing its signal transduction mechanisms and evaluating its biological functions.

VI. Conclusion.

In response to the needs of FGF-23 function research and detection method development, UniAll provides FGF-23 Protein, Human. This product is suitable for application scenarios such as binding activity analysis of FGF-23 with the FGFR1c/Klotho receptor complex, research on the signaling pathway mechanisms of FGF-23 in CKD-MBD, establishment and validation of FGF-23 immunoassay methods, and evaluation of therapeutic strategies targeting FGF-23.

As a core regulatory factor in mineral metabolism disorders of chronic kidney disease, FGF-23 has become a novel biomarker and therapeutic target of great interest in the field of CKD diagnosis and treatment, owing to its multiple clinical values as the earliest appearing detection indicator of CKD-MBD, its formation of a signaling axis with Klotho to participate in CKD progression, and its role as a predictor of cardiovascular events. From the complex interactions between FGF-23 and calcium-phosphorus metabolism to the pathophysiological significance of the Klotho/FGF-23 signaling axis, from an early biological marker of CKD to the construction of comprehensive diagnosis and treatment strategies, FGF-23 continues to drive the in-depth development of the field of nephrology. FGF-23 Protein, Human provides reliable tool support for mechanistic research on the FGF-23 signaling network and the development of related diagnosis and treatment strategies, and will continue to facilitate innovative exploration in the field of precision diagnosis and treatment of chronic kidney disease.

This article is reviewed and published by the technical expert team of UA

Disclaimer: This article partially utilizes artificial intelligence assistance in its creation. If any content involves copyright or intellectual property issues, please let us know and we promise to verify and remove it as soon as possible.

Purchase recombinant protein, choose

UA protein focuses on providing various protein reagents, raw materials, and services required for drug research and development, cell therapy, gene therapy, and basic scientific research, including drug target proteins, immune checkpoint proteins, cytokines, tool enzymes, customized protein expression, and full-length transmembrane protein development. Nanjing Univ is committed to providing customers with high-quality products and professional services, and building a High-tech Biological Enterprise with International Competitiveness.

Buy antibodiesFind UA www.ua-bio.com | 15 years of protein development experience

Nanjing UNIV Biotechnology Co., Ltd. Email：order@ua-bio.com Phone：+86-25-56221161

more products

Product Information

The Last The Next