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INTRODUCTION AND IMPORTANCE: The median arcuate ligament syndrome (MALS) is a rare disorder that produces a spectrum of symptoms due to compression of the arcuate ligament, clinically manifested primarily by abdominal pain, nausea, vomiting, and weight loss. The mechanism of these symptoms has not yet been revealed, and the current treatment methods are still somewhat controversial. CASE PRESENTATION: We present a 54-year-old woman who presented with intermittent epigastric pain for nine months. During the onset, she lost 7.5 kg. After routine examinations in a nearby hospital, no abnormality was found. She was referred to us. CTA showed compression of the celiac artery. Further selective celiac angiography at the end of inspiration and expiration confirmed MALS. After consultation with the patient, the decision to have a laparotomy was made. The celiac artery was completely skeletonized, and external compression on the artery was released. Postoperative symptoms improved significantly. One-year follow-up after the operation, she had a weight gain of 4.8 kg and was satisfied with the surgical results. CLINICAL DISCUSSION: The manifestations of MALS are varied and challenging. Our patient presented with weight loss and intermittent abdominal pain. The mutual confirmation of multiple investigations can provide a more comprehensive overview of celiac artery compression. We confirmed using ultrasonography, CT angiography, and selective digital subtraction angiography in this case. The celiac artery compression was relieved after open surgery. Our patient's symptoms improved significantly after surgery. We hope our treatment method can provide a reference for MALS diagnosis and treatment. CONCLUSION: It is challenging to diagnose MALS. Cross-confirmation of multiple examinations can provide a more comprehensive view of celiac compression. Surgical decompression of the celiac artery (open or laparoscopic surgery) may be an effective therapy for MALS, especially in centers with experience.
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This study aims to discover the therapeutic effect of chemokine (CXC motif) receptor 4 (CXCR4) antagonist AMD3100 combined with transcatheter arterial chemoembolization (TACE) in a rat model with hepatocellular carcinoma (HCC). An orthotopic model of HCC was established and treated with TACE (doxorubicin-lipiodol emulsion) with or without AMD3100. The tumor volume was measured by magnetic resonance imaging (MRI). Histopathological changes were detected by hematoxylin-eosin (HE) staining. HCC cell apoptosis was assessed by terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) staining. Immunohistochemistry was used to detect the expression of CD34, hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and Ki67. Gene and protein expressions were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. Both TACE and AMD3100 reduced the tumor volume in orthotopic rat model of HCC with the decreased CXCR4 expression in tumor tissues, and the combination had better effect. However, TACE increased the microvessel density (MVD) in HCC tissues of rats, while AMD3100 treatment reduced MVD in HCC tissues. AMD3100 reduced the TACE induced MVD in HCC tissues with the reduction of HIF-1α and VEGF expression. Either AMD3100 or TACE could promote HCC cell apoptosis accompanying by decreased cell proliferation, and their combined use had better therapeutic effects. CXCR4 antagonist AMD3100 enhance therapeutic efficacy of TACE in rats with HCC via promoting the HCC cell apoptosis, reducing cell proliferation, and inhibiting MVD, thus reducing tumor volume.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Animales , Bencilaminas , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Quimioembolización Terapéutica/métodos , Ciclamas , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Ratas , Receptores CXCR4/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The true extent of a tumor is difficult to visualize, during radiotherapy, using current modalities. In the present study, the safety and feasibility of a mixture of N-butyl cyanoacrylate and lipiodol (NBCA/Lip) was evaluated in order to investigate the optimal combination for application as a fiducial marker for radiotherapy. Four combinations of NBCA/Lip injection (1:1-0.1, 1:1-0.15, 1:3-0.1 and 1:3-0.15 ml) were injected into the subcutaneous tissue of BALB/c mice. The changes in gross histopathology, body weight, skin score, marker volume, neutrophil and macrophage counts were observed to analyze the effects of the different mixing ratios and injection volumes, in order to identify the best combination. Evaluation according to the International Organization for Standardization criteria was further conducted in order to test the biocompatibility of the mixture, including an acute systematic assay with mice, cytotoxicity with L929 fibroblasts and delayed-type hypersensitivity tests with guinea pigs and an intradermal test with rabbits. The results revealed that at the seventh week, 42 markers (42/48; 87.5%) were still visible using computed tomography (CT) imaging. No serious adverse effects were observed throughout the study period; however, the combination of 1:1-0.1 ml had the lowest body weight and worst skin score. A review of the histopathological reaction to NBCA/Lip revealed a combination of acute inflammation, chronic inflammation, granulation tissue, foreign-body reaction and fibrous capsule formation. The 1:1 NBCA combination ratio resulted in the most intense tissue repair reaction and a slower degradation rate of markers. In general, the combination of 1:3-0.15 ml had a better fusion with local tissue, maintained a stable imaging nodule on CT images for 7 weeks and the final biocompatibility test demonstrated its safety. Overall, the findings of the present study demonstrated NBCA/Lip as a safe and feasible fiducial marker, when using the 1:3-0.15 ml combination.
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An understanding of the interaction between the antibody and its targeted antigen and knowing of the epitopes are critical for the development of monoclonal antibody drugs. Complement factor H (CFH) is implied to play a role in tumor growth and metastasis. An autoantibody to CHF is associated with anti-tumor cell activity. The interaction of a human monoclonal antibody Ab42 that was isolated from a cancer patient with CFH polypeptide (pCFH) antigen was analyzed by molecular docking, molecular dynamics (MD) simulation, free energy calculation, and computational alanine scanning (CAS). Experimental alanine scanning (EAS) was then carried out to verify the results of the theoretical calculation. Our results demonstrated that the Ab42 antibody interacts with pCFH by hydrogen bonds through the Tyr315, Ser100, Gly33, and Tyr53 residues on the complementarity-determining regions (CDRs), respectively, with the amino acid residues of Pro441, Ile442, Asp443, Asn444, Ile447, and Thr448 on the pCFH antigen. In conclusion, this study has explored the mechanism of interaction between Ab42 antibody and its targeted antigen by both theoretical and experimental analysis. Our results have important theoretical significance for the design and development of relevant antibody drugs.
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Anticuerpos Monoclonales/inmunología , Péptidos/inmunología , Anticuerpos Monoclonales/química , Reacciones Antígeno-Anticuerpo , Autoanticuerpos/química , Autoanticuerpos/inmunología , Factor H de Complemento/química , Factor H de Complemento/inmunología , Regiones Determinantes de Complementariedad/química , Regiones Determinantes de Complementariedad/inmunología , Epítopos/química , Epítopos/inmunología , Humanos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Neoplasias/inmunología , Péptidos/química , Conformación ProteicaRESUMEN
INTRODUCTION AND AIM: To investigate the effect of mTOR inhibitor Rapamycin combined with transcatheter arterial embolization (TAE) on the growth, metastasis, and prognosis of hepatocellular carcinoma (HCC) in rat model. MATERIAL AND METHOD: McARH7777 cells were used to construct rat models of HCC, which were randomly divided into Model, Rapamycin, TAE, and Rapamycin + TAE groups. Quantitative reverse transcription-PCR (qRT-PCR) and Western Blot were used to detect the expression of Epithelial-Mesenchymal Transition (EMT)-related molecules, and immunohistochemical staining to determine the expression of EMTrelated proteins, angiogenic factors as well as microvessel density (MVD)-CD34. RESULTS: The hepatic tumor volume of rats in the other three groups were all significantly smaller than the Model group on the 7th, 14th, and 21st day after treatment and the combination treatment was apparently more effective than either treatment alone. Besides, both the number and the size of metastatic nodules of HCC rats after combination treatment were remarkably reduced. In addition, compared with rats in the Rapamycin + TAE group, N-cadherin, Vimentin, HIF-1α, VEGF, and MVD-CD34 were obviously enhanced, while E-cadherin was lowered in those TAE group, which were the complete opposite to the Rapamycin group. Besides, the median survival time of rats in the Rapamycin + TAE group was evidently longer than the resting groups. CONCLUSION: Rapamycin combined with TAE may effectively suppress the EMT formation and angiogenesis, thereby inhibiting the growth and lung metastasis of HCC rats, which provides a new idea for countering the recurrence and metastasis of HCC.
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Antibióticos Antineoplásicos/farmacología , Carcinoma Hepatocelular/terapia , Proliferación Celular/efectos de los fármacos , Embolización Terapéutica , Neoplasias Hepáticas Experimentales/terapia , Neoplasias Pulmonares/terapia , Sirolimus/farmacología , Animales , Antígenos CD34/metabolismo , Cadherinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/secundario , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Masculino , Neovascularización Patológica , Proteínas del Tejido Nervioso/metabolismo , Ratas Endogámicas BUF , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo , Carga Tumoral/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Vimentina/metabolismoRESUMEN
Chemotherapy has limited efficacy in the treatment of advanced and metastatic pancreatic cancer (PC), and has serious side effects. The development of novel effective agents, especially targeted therapy, is essential for patients with PC. We present a 58-year-old Chinese woman initially diagnosed with locally advanced PC. As the disease progressed to Stage IV, the patient was unable to tolerate chemotherapy after the fourth-line treatment. She was then treated with apatinib, a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 and achieved a progression-free-survival of 7 mo. All drug-related side effects were well controlled with medication. To the best of our knowledge, this is the first case of PC which responded to apatinib. Considering this remarkable response, apatinib may be a promising agent in the treatment of PC. We also reviewed the literature on chemotherapy and targeted therapy, especially the anti-angiogenesis therapy for patients with PC, and investigated the effect of apatinib in other solid tumors as well.
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Neoplasias Pancreáticas/terapia , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Inhibidores de la Angiogénesis/uso terapéutico , Antígenos de Carbohidratos Asociados a Tumores/sangre , Quimioradioterapia/métodos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Resultado Fatal , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Derrame Pleural Maligno/diagnóstico por imagen , Derrame Pleural Maligno/tratamiento farmacológico , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Insuficiencia del Tratamiento , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , GemcitabinaRESUMEN
In this paper, we demonstrate a compact electrically pumped distributed-feedback hybrid III-V/silicon laser with laterally coupled Bragg grating for the first time to the best of our knowledge. The hybrid laser structure consists of AlGaInAs/InP multi-quantum-well gain layers on top of a laterally corrugated silicon waveguide patterned on a silicon on insulator (SOI) substrate. A pair of surface couplers is integrated at the two ends of the silicon waveguide for the optical coupling and characterization of the ouput light. Single wavelength emission of ~1.55µm with a side-mode-suppression- ratio larger than 20dB and low threshold current density of 1.54kA/cm(2) were achieved for the device under pulsed operation at 20 °C.
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Selenium (Se) is an important dietary micronutrient with antioxidative roles. Cadmium (Cd), a ubiquitous environmental pollutant, is known to cause brain lesion in rats and humans. However, little is reported about the deleterious effects of subchronic Cd exposure on the brain of poultry and the protective roles on the brain by Se against Cd. The aim of this study was to investigate the protective effects of Se on Cd-induced brain damage in chickens. One hundred twenty 100-day-old chickens were randomly assigned to four groups and were fed a basal diet, or Se (as 10 mg Na2SeO3/kg dry weight of feed), Cd (as 150 mg CdCl2/kg dry weight of feed), or Cd + Se in their basic diets for 60 days. Then, concentrations of Cd and Se, production of nitric oxide (NO), messenger RNA (mRNA) level and activity of inducible NO synthase (iNOS), level of oxidative stress, and histological and ultrastructural changes of the cerebrum and cerebellum were examined. The results showed that Cd exposure significantly increased Cd accumulation, NO production, iNOS activities, iNOS mRNA level, and MDA content in the cerebrum and cerebellum. Cd treatment obviously decreased Se content and antioxidase activities and caused histopathological changes in the cerebrum and cerebellum. Se supplementation during dietary Cd obviously reduced Cd accumulation, NO production, mRNA level and activity of iNOS, oxidative stress, and histopathological damage in the cerebrum and cerebellum of chickens. It indicated that Se ameliorates Cd-induced brain damage in chickens by regulating iNOS-NO system changes, and oxidative stress induced by Cd and Se can serve as a potential therapeutic for Cd-induced brain lesion of chickens.
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Daño Encefálico Crónico/inducido químicamente , Daño Encefálico Crónico/prevención & control , Cadmio/toxicidad , Selenio/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Encéfalo/metabolismo , Daño Encefálico Crónico/enzimología , Daño Encefálico Crónico/metabolismo , Cadmio/administración & dosificación , Pollos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , Selenio/administración & dosificaciónRESUMEN
Alpha-1-antitrypsin (A1PI) is a proteinase inhibitor of the serpin superfamily and circulates in plasma at about 1-2 g/L. A1PI deficiency in humans often results in organ damage, particularly to the lungs and liver. Current augmentation therapies rely entirely on A1PI isolated from human plasma, thus prompting an evaluation of alternate sources. We have co-expressed recombinant A1PI and α-2,3-sialyltransferase in the human cell line, PER.C6. The requirement for sialyltransferase overexpression in PER.C6 and the essential contribution of sialic acid glycan capping on pdA1PI and recA1PI to prevent rapid A1PI plasma elimination is shown. Using assays to predict high levels of A1PI production and sialylation, stably transfected PER.C6 cells were screened through two rounds of cell cloning to ensure monoclonality. Fed-batch culturing was used to evaluate recA1PI production and cell line characteristics, identifying subclones expressing over 2.5 g/L recA1PI. Cell stability was assessed over 50 generations, verifying subclone stability during continuous culture. Finally, data are presented showing that recA1PI and pdA1PI are equivalent in their ability to block elastase activity in functional cell-based assays and their pharmacokinetic properties. These data show that recombinant human A1PI recovered from PER.C6 cells offers a reliable source of functionally active A1PI for augmentation therapies and, potentially, other diseases.
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Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , alfa 1-Antitripsina/biosíntesis , alfa 1-Antitripsina/química , Animales , Línea Celular , Semivida , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Ácido N-Acetilneuramínico/metabolismo , Estabilidad Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacocinética , Sialiltransferasas/genética , Sialiltransferasas/metabolismo , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/farmacocinéticaRESUMEN
A nanosecond 1.3 microm Nd:YAG laser-pumped external cavity eye-safe Raman laser based on BaWO(4) crystal is efficiently demonstrated. The average power of 1.5 microm was 0.60 W operating at a pulse repetition rate of 1.7 kHz and an incident pump power of 4.14 W. Conversion efficiency of 14.5% and a high slope efficiency of 54.5% have been achieved. Pulse shortening was obviously observed. The pulse duration of the first Stokes was about 40 ns, much shorter than the fundamental pulse with a duration of approximately 220 ns.
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Compuestos de Bario/química , Cristalización/métodos , Rayos Láser , Espectrometría Raman/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Lesiones Oculares/prevención & controlRESUMEN
The stimulation and maintenance of the pulmonary alveolar type II cell's capacity to biosynthesize, store, and secrete surfactant proteins (SPs) are modulated to a great extent by growth factors, extracellular matrix (ECM) components, and hormones. It is possible that differences in ECM composition, as exist between type I and II cells normally or as might occur with excessive cell surface shedding during inflammation or injury states, may specifically alter SP expression. Here, isolated type II cells were exposed to the model sulfated ECM heparin; desulfated heparin; and/or fibroblast growth factor (FGF)-1, -2, or -7 for 24 h to examine by quantitative real-time polymerase chain reaction their effects on SP gene expression. Aquaporin 5 (AQP-5) gene expression was also examined as a phenotypic marker for the type I cell. SP-B mRNA abundance was increased 4- to 8-fold by all three FGFs. Heparin at low concentrations (5 microg/ml) or desulfated heparin at high concentrations (500 microg/ml) enhanced the effects of FGF-2 and -7, while high heparin concentrations (500 microg/ml) were inhibitory. In contrast, SP-B mRNA abundance was increased by heparin in a dose- and sulfation-dependent manner when used in combination with FGF-1. SP-C and AQP-5 mRNA levels were increased by heparin alone in a dose- and sulfation-dependent manner, while all FGFs lacked effect on SP-C or AQP-5 mRNA levels. These data indicate that heparin can be stimulatory to SP gene expression depending on concentration, degree of sulfation, and surrounding FGF environment, and that heparin plays a significant role in modulating alveolar epithelial cell phenotype in vitro.
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Factores de Crecimiento de Fibroblastos/metabolismo , Regulación de la Expresión Génica , Heparina/metabolismo , Péptidos , Alveolos Pulmonares/citología , Proteína B Asociada a Surfactante Pulmonar , Animales , Acuaporina 5/genética , Acuaporina 5/metabolismo , Células Cultivadas , Matriz Extracelular/química , Péptidos/genética , Péptidos/metabolismo , Alveolos Pulmonares/fisiología , Proteína B Asociada a Surfactante Pulmonar/genética , Proteína B Asociada a Surfactante Pulmonar/metabolismo , Surfactantes Pulmonares/metabolismo , Ratas , Ratas Endogámicas F344 , Sulfatos/metabolismoRESUMEN
Undersulfation of the basement membrane matrix of alveolar type II (AT2) cells compared with that of neighboring type I cells is believed to account for some of the known morphological and functional differences between these pneumocytes. Heparin, a model for sulfated components of basement membrane matrices, is known to inhibit fibroblast growth factor (FGF)-2-stimulated DNA synthesis as well as gene expression of FGF-2 and its receptor in AT2 cells. To determine whether these end points result from specific effects of heparin on FGF-related signaling pathways, isolated rat AT2 cells were treated with 100 ng/ml FGF-1 or FGF-2 in the presence of up to 500 microg/ml heparin. In addition, experiments were done on cells grown in the presence of 20 mM sodium chlorate (sulfation inhibitor). High-dose heparin reduced FGF-1- or FGF-2-stimulated phosphorylation of mitogen-activated protein kinase kinases (MEK1/2), p44/42 mitogen-activated protein kinases (MAPK/ERK1/2), stress-activated protein kinase/c-Jun NH(2)-terminal kinase, Akt/protein kinase B, and p90(RSK). FGF-2-stimulated signaling was more sensitive to heparin's effects than was signaling stimulated by FGF-1. Heparin had an additive effect on the reduced [(3)H]thymidine incorporation in FGF-2-treated AT2 cells caused by inhibition of the MEK/ERK pathway by the MEK inhibitor PD-98059. The data suggest that heparin's known capacity to alter DNA synthesis and, possibly, other biological end points is realized via cross talk between multiple signaling pathways.
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Factor 1 de Crecimiento de Fibroblastos/farmacología , Factor 2 de Crecimiento de Fibroblastos/farmacología , Heparina/farmacología , Proteínas Serina-Treonina Quinasas , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/fisiología , Transducción de Señal/efectos de los fármacos , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Heparina/administración & dosificación , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Alveolos Pulmonares/citología , Alveolos Pulmonares/metabolismo , Ratas , Ratas Endogámicas , Sulfatos/metabolismo , Timidina/metabolismo , Factores de TiempoAsunto(s)
Modulación Antigénica/genética , Modulación Antigénica/inmunología , Asma/genética , Asma/inmunología , Células Epiteliales/inmunología , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/inmunología , Expresión Génica/genética , Expresión Génica/inmunología , Transducción de Señal/genética , Transducción de Señal/inmunología , Humanos , Técnicas In VitroRESUMEN
Responses of isolated type II alveolar cells to fibroblast growth factors (FGF) have been shown to be sensitive to the level of sulfation in extracellular matrix (ECM) substrata. These observations may reflect the specific in situ distribution and level of sulfation of ECM within the alveolar basement membranes (ABM) associated with type II cells. The goal of this study was to determine if the model sulfated ECM heparin modified DNA synthesis and gene expression by type II cells in a concentration dependent-manner. Isolated rat type II cells were exposed to different concentrations of heparin (0.005-500 micro g/ml) in serum-free medium for 1-3 d with or without FGF-1 or FGF-2. The effects of heparin were examined by [(3)H]thymidine incorporation into DNA, total cell protein, cell number, and selected gene expression. Results indicated that heparin inhibited [(3)H]thymidine uptake in a concentration-dependent manner. Total protein, cell number, and FGF-2 protein expression and mRNA of FGF-1, -2, and FGF receptor-2 detected by reverse transcriptase-polymerase chain reaction were decreased by heparin. These results demonstrate that sulfated molecules in the ABM may play important regulatory role(s) in selected type II cell activities during normal cell homeostasis, turnover, and repair after lung injury.
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ADN/biosíntesis , Expresión Génica/efectos de los fármacos , Heparina/farmacología , Alveolos Pulmonares/citología , Alveolos Pulmonares/efectos de los fármacos , Animales , División Celular/efectos de los fármacos , Células Cultivadas , ADN/efectos de los fármacos , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Factor 1 de Crecimiento de Fibroblastos/genética , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Factor 1 de Crecimiento de Fibroblastos/farmacología , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/farmacología , Alveolos Pulmonares/fisiología , Ratas , Ratas Endogámicas F344 , Proteínas Tirosina Quinasas Receptoras/efectos de los fármacos , Proteínas Tirosina Quinasas Receptoras/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , Receptores de Factores de Crecimiento de Fibroblastos/efectos de los fármacos , Receptores de Factores de Crecimiento de Fibroblastos/genética , Timidina/metabolismoRESUMEN
Type II cells attach, migrate, and proliferate on a provisional fibronectin-rich matrix during alveolar wall repair after lung injury. The combination of cell-substratum interactions via integrin receptors and exposure to local growth factors are likely to initiate the signals required for cell proliferation, differentiation, reepithelialization, and ultimate restoration of the alveolar wall structure. Accordingly, primary cultured type II cells have been shown to bind fibronectin, in part through the alpha5beta1 integrin, and to respond to growth factors that induce type II cell proliferation, such as fibroblast growth factor 1 (FGF-1). The purpose of this study was to determine whether or not FGF-1 modifies type II cell attachment to fibronectin, and if together they affect DNA synthesis. Attachment assays showed that FGF-1 treatment enhanced type II cell adhesion to fibronectin. This effect correlated with an increase in beta1 integrin cell surface expression, and with the formation of cytoskeletal stabilizing structures such as lamellipodial extensions and stress fibers. FGF-1 also induced an increase in thymidine incorporation into DNA. Together FGF-1 and fibronectin appear to promote adhesion, cytoskeletal organization, and increased DNA synthesis, and in this way influence cell-substratum interactions and signaling during alveolar repair.