Efecto del factor de crecimiento de fibroblastos 21 / Fibroblast growht factor 21 effects over phosphatase SHP-2 expression in Malme-3 cells

Almost 50 percent of Noonan syndrome patients, characterized by short stature, present activating mutations of the citoplasmatic phosphatase SHP-2, which induce hyperactivation of the Ras/MAPK pathway. On the other hand, the fibroblast growth factor 21 (FGF-21), recently suggested as a FGF with “endocrine” function, would affect longitudinal growth inhibiting growth hormone signaling at chondrocytes level. Union and activation of FGF-21 to its receptor is regulated by the co-factor beta Klotho (KLB). Aims: To determine if FGF-21 and/or FGF-21+KLB are able to modify the genetic expression of SHP-2 ina human skin fibroblast cell line (Malme-3). Methods: cells were incubated with or without FGF-21, FGF-21 + KLB. At 12 and 24 hours after induction total RNA was extracted andSHP-2 mRNA levels were determine by quantitative PCR. Expression of GADPH gene was employed for normalization. Results: Incubation with FGF-21 produce a 36 percent (p = < 0,05)increment in SHP-2 expression, which was not modified with KLB co-incubation. Discussion: it is shown by the first time that FGF-21 is able to produce an increase in SHP-2 gene expression in human fibroblast, which was independent of KLB presence...

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.

Efectos de los factores de crecimiento sobre el hueso: sus implicancias para la implantología / Effects of growth factors on the bone: its implications for implantology

El control localizado de la masa ósea puede requerir la creación de nuevo hueso. La biotecnología nos permite acceder a moléculas que son determinantes en su generación. Aprender a emplear las formas recombinadas de estas moléculas puede permitirnos controlar clínicamente la cantidad de hueso disponible para mejorar la colocación de implantes en lugares con deficiencias óseas

Role of cytokines, prostaglandins and nitric oxide in hepatic regeneration

The liver is considered the center of the metabolism. Many of its functions are controlled by a network of mediators. Hepatic regeneration is a highly regulated event also by several substances. Herein is was reviewed the literature about the role of cytokines, prostaglandins and nitric oxide in this event. Prior, it was described the known activities of each substance in the body. Further, it was examined since the production until the action of each one in regenerating livers. We could conclude that some of these mediators present a well-defined action, while others are object of great controversy. Overall, the comprehension of the liver's regeneration is very important in concern to develop new kinds of treatment in hepatology.

Patogênese da nefropatia diabética: o papel das citocinas / Pathogenesis of diabetic nephropathy: citokines role

Os autores abordam a patogênese da nefropatia diabética (ND) em seus aspectos hemodinâmicos-renais e metabólicos, com ênfase na formaçäo da matriz extra celular (MEC). O aumento da pressäo capilar intra-glomerular é um fator patogenético bem estabelecido, mas seu mecanismo de lesäo, embora desconhecido, pode envolver distensäo glomerular, levando a um aumento da produçäo de MEC. Existe entretanto um efeito direto da glicose, observado em glomérulos in vitro, onde altas concentraçöes de glicose estimulam o aumento de síntese da MEC. Este efeito pode ser tanto direto, via ativaçäo da proteina quinase C, como indireto pela formaçäo de produtos de glicosilaçäo nao-enzimática ou pela ativaçao da via dos polióis. O TGF-beta (Transforming Growth Factor Beta) é uma citocina que promove aumento de síntese e a reduçäo da degradaçao da MEC, levando ao acúmulo desta. Aumentos dos níveis de RNAm para TGF-beta no glomérulo de ratos diabéticos já foram documentados nas fases iniciais da ND experimental e a presença de reaçäo imunohistoquímica para TGF-beta já foi detectada em ratos e em pacientes com ND estabelecida. O TGF-beta também regula, in vitro, o aumento de síntese de MEC induzido pela angiotensina II e pelo tromboxane A2. A IGF-1 (Insulin Growth Factor-1) pode ter papel significativo na hipertrofia renal diabética, enquanto que o TNF-alpha (Tumor Necrosis Factor) participa na regulaçäo do aumento da permeabilidade do endotélio glomerular. As demais citocinas (EGF, FGF, IL-1, PDGF e TGF-a) ainda precisam ser melhor estudadas.

Structure and function of fibroblast growth factor

We describe some structural requirements od the fibroblast growth factor (FGF) signaling system for the stimulation of the mitogenic response in terms of the design, synthesis and mitogenic activity of linear peptides related to the human FGF-1 sequence and the structural requirements of heparin for the potentiation of the mitogenic activity of FGF-1. The best mitogenic peptide we have synthesized so far is Ac-WFVGLKKNGSSKRGPRT-NH2, that has been shown: 1)to bind to heparin-Sepharose columns with moderate affinity, requiring about 0.5 M NaCl to be eluted from the resin; 2) to be mitogenic upon BALB/c 3T3 fibroblasts in culture (ED50=10-20 muM) and 3)to compete with human FGF-1 for cellular binding (ID50=30-50 muM). The potentiating activity of heparin upon FGF-1 has shown to be dependent on the oligosaccharide size, degree of sulfation and carboxylation. Apparently, these same requirements hold for the heparan sulfate molecules. Based on the reported studies, ee propose some important requirements of an oligosaccharide to potentiate FGF-1 mitogenic activity: 1) to have a minimum of twelve units, organized as disaccharides where one of the units is a uronic acid and the second is glycosamine; 2) to have at least one iduronic acid sulfated at position 2 and 3) to have N-sulfated glycosamines, preferentially 6-O-sulfated. To have groups of negative charges is not enough: they need to be localized in a correct conformation.

El factor de crecimiento neural en el sistema nervioso central / Nerve growth factor in the central nervous system

El factor de crecimiento neuronal (FCN), miembro de la familia de las neurotrofinas, es una proteína que desempeña un papel decisivo en la sobrevivencia y metabolismo de las neuronas colinérgicas del sistema nervioso central (SNC). Debido a que el sistema colinérgico del SNC ha sido involucrado en los procesos de aprendizaje y memoria, durante la última década se han puesto en práctica varios procedimientos experimentales con la finalidad de administrar el FCN en el SCN. Simultáneamente se han registrado importantes avances en el conocimiento de las características inherentes a la estructura así como a los mecanismos de acción y biosíntesis de esta molécula. La presente revisión intenta mostrar un panorama global acerca del estado actual de las investigaciones en torno a estos temas

Metabolismo del hueso periodontal: Parte IV. Control local del metabolismo de hueso / Periodontal bone metabolism: Part IV. Local control of bone metabolism

El presente trabajo es el cuarto de una serie de 5 artículos dedicados al estudio del metabolismo del hueso periodontal. En los tres primeros se hizo una descripción de la biología celular del hueso periodontal, de los fenómenos fisiológicos que se encadenan en el ciclo de remodelado óseo y del control sistémico del metabolismo de hueso. El objetivo del presente trabajo es el de presentar una revisión actualizada sobre las diversas sustancias que intervienen en el control local de la fisiología del hueso periodontal. Aunque varían los criterios de clasificación, se puede decir que cuatro familias de sustancias se encargan del control local del metabolismo de hueso: los factores de crecimiento, las monoquinas, las linfoquinas y los derivados del ácido arachidónico (AA). La compleja interacción de estas sustancias entre sí y con respecto a las hormonas osteotrópicas es un fiel reflejo de que la reabsorción y aposición óseas son fenómenos complejos regulados por un estricto control local