FGF-23: estado da arte / FGF-23: state of the art

Há aproximadamente 10 anos descobriuse um hormônio denominado FGF-23 (fator de crescimento de fibroblastos 23), um membro da família dos fatores de crescimento de fibroblastos, cujas funções atualmente conhecidas envolvem o metabolismo do fósforo (P) e a inibição da 1α hidroxilase, enzima responsável pela síntese de calcitriol. Tal descoberta possibilitou um novo entendimento sobre os mecanismos de controle do P, um elemento associado com mortalidade, especialmente na doença renal crônica (DRC). Nesta revisão descreveremos diversos aspectos deste hormônio, desde a sua descoberta, função, produção, mecanismo de ação, até os últimos estudos clínicos envolvendo o mesmo. Posteriormente, abordaremos as possíveis repercussões destes estudos na prática clínica.

Approximately 10 years ago, a member of the family of the fibroblast growth factors, the hormone FGF-23 (fibroblast growth factor 23) was discovered. Its currently known functions involve phosphorus (P) metabolism and inhibition of 1αhydroxylase, the enzyme responsible for the synthesis of calcitriol. That discovery led to a better understanding of the mechanisms of P control, an element associated with mortality, especially in chronic kidney disease. This study reviews several aspects of that hormone, such as its discovery, function, production, mechanism of action, and the most recent clinical studies about it. Afterwards, a discussion about the possible effects of those studies on clinical practice will be presented.

Changes of fibroblast growth factor-21 and its receptors in high-fat diet fed apoE~(-/-) mice / 中华内分泌代谢杂志

Objective To investigate the effects of high-fat diet induced insulin resistance on fibroblast growth factor-21 (FGF-21) and its receptors expression in ApoE~(-/-) mice. Method Male ApoE~(-/-) mice were randomly divided into normal-chow group(NF,n=20)and high-fat fed group(HF,n=20) and fed for 16 weeks. The insulin sensitivity and glucose-lipid metabolism in awake mice were evaluated by hyperinsulinemic-euglycemic clamp technique combined with 3-[~3H]-glucose as a tracer. The Mrna expressions of FGF-21,β-klotho, and FGFR1-4 were measured by quantitative real-time PCR. FGF-21 protein levels were determined by Western blot. Results Fasting blood glucose, plasma insulin and free fatty acids, triglycerides, free fatty acids, and cholesterols were significantly elevated in HF group compared with NF group(all P<0.01). During the steady-state of clamp, plasma insulin was significantly higher in HF group than that in NF group(P<0.01), and glucose infusion rate was also significantly decreased(P<0.01). At the end of insulin clamp, glucose disappearance rate was significantly lower in HF group than that in NF groups(P<0.01). Hepatic glucose production in NF group was suppressed by 70% ,while in HF group it was suppressed by 51%. The FGF-21 Mrna expressions of hepatic and adipose tissues in HF group were significantly increased compared with NF group(both P<0.01), and β-klotho Mrna expressions increased(P<0. 05). In hepatic and adipose tissues, FGFRI, Mrna expressions were higher in HF group than those in NF group(both P<0.01) ,and FGFR3 Mrna increased(P<0.01 and P<0.05, respectively). In hepatic tissue,FGFR4 Mrna levels were significantly up-regulated in HF group(P<0. 05). Plasma FGF-21 levels were elevated in HF group compared with NF group(P<0.01) ,and FGF-21 protein expressions of hepatic and adipose tissues were also increased(both P<0.05). Conclusion FGF-21, β-klotho, FGFR1, and FGFR3 were significantly up-regulated in ApoE~(-/-) mice fed by high-fat diet, and they might be the targets in regulating glucose-lipid metabolism by FGF-21.

Roles of basic fibroblast growth factor in the seft-renewal of human embryonic stem cells / 国际生物医学工程杂志

The self-renewal and multi-lineage developmental potential are the unique properties of human embryonic stem(ES) cells. The growth factors that maintain human or mouse embryonic stem cells are different. Leuckemia inhibitory factor(LIF) does not maintain self-renewal of human ES cells(hESCs). Recently, a few growth factors have been found to be biologically relevant for hESCs functions in vitro, among them the basic fibroblast growth factor(bFGF) is one of the most significant regulators of hESCs self-renewal. The purpose of this review is to introduce the recent progress in the research on the expressions of bFGF and its receptors and their functions in hESCs.

Significance of bFGF,FGFR-2 and Hpa expression in gastric precancerous lesions and gastric carcinoma tissues / 中国实用内科杂志

Objective To study the expression of basic fibroblast growth factor(bFGF),fibroblast growth factor receptor-2(FGFR-2)and heparanase(Hpa)in the tissues of gastric cancer and precancerous lesions,and to explore its significance in the carcinogenesis and malignant progression of stomach.Methods The expression of bFGF,FGFR-2 and Hpa were detected by immunohistochemistry in 145 cases of paraffin-embedded specimens from different gastric mucosa,including 30 cases of chronic superficial gastritis(CSG),29 of intestinal metaplasia(IM),31 of dysplasia(Dys)and 55 of gastric carcinoma(GC).Results The expression of bFGF and FGFR-2 in CSG group was significantly lower than that of the other three groups(P

Moleculobiological Analysis of Fibroblast Growth Factor Receptors in Korean Patients with Craniosynostosis

Fibroblast growth factor(FGF) play a critical role in bone growth and development, affecting both chondrogenesis and osteogenesis. The authors believe, many craniosynostosis disorders to be linked with activating mutations in the fibroblast growth factor receptors (FGFRs). In recent studies, detected mutations of the FGFR gene has been reported in some syndromic craniosynostosis patients. So far sequence analysis of FGFR in syndromic craniosynostosis has been reported in many Caucasian patients. But Asian patients, especially in Koreans, only several cases were reported. The authors performed a prospective study, evaluating molecular diagnosis of FGFR 1, 2 and 3 in six Korean patients with craniosynostosis(four with isolated craniosynostosis and two with craniosynostosis syndrome) and four normal child as a control group, by polymerase chain reaction(PCR) followed by direct sequencing methods. The results did not demonstrate, any mutation in normal child but mutations in all six patients with craniosynostosis were seen. Three of four patients with isolated craniosynostosis carried mutation in exon 5 of FGFR 1 and exon 10 of FGFR 3 and two patients with craniofacial synostosis syndrome in exon 7, 10 of FGFR 3. Mutation for the same amino acid residue on FGFRs was not found. But two patients with isolated craniosynostosis and one patient with craniofacial synostosis syndrome had the same mutation pattern in exon 10 of FGFR 3 (Met363Val). Then more investigative attempts are needed to correlate a craniosynostosis and mutation in FGFRs with a large sample of patients.