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1.
Food Chem ; 308: 125576, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31648092

RESUMO

This study investigated the effects of cold storage at different temperatures (4, -0.5, -3, and -20 °C) on protein degradation and its relationship to structural changes of black carp muscle. At -0.5 and 4 °C, major structural changes occurred, including the formation of gaps between myofibers and myofibrils, breakage of myofibrils and myofibers, and degradation of sarcoplasmic reticulum. Gel-based proteomic analysis showed that these structural changes were accompanied by degradation of a series of myofibrillar proteins, including titin, nebulin, troponin, myosin, myomesin, myosin-binding protein, and α-actinin. Loss of extractable gelatinolytic and caseinolytic protease activities was also observed. At -3 and -20 °C, formation of ice crystals was the most noticeable change. The major proteins were degraded at different locations in the black carp muscle, and gelatinolytic and caseinolytic proteases appear to contribute to the degradation of those proteins.


Assuntos
Carpas/metabolismo , Actinina/metabolismo , Animais , Proteínas de Transporte , Temperatura Baixa , Conectina/metabolismo , Cyprinidae/metabolismo , Proteínas Musculares/metabolismo , Miofibrilas/metabolismo , Miosinas/metabolismo , Proteólise , Proteômica
2.
Mol Med Rep ; 20(4): 3617-3624, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485649

RESUMO

It has been reported that loss and degradation of epidermal melanocytes is closely associated with the pathogenesis of vitiligo. In addition, CD8+ T and regulatory T (Treg) cells serve an important role during these two processes. MicroRNA­155 (miR­155) is known to contribute to the pathogenesis of vitiligo; however, the mechanism by which miR­155 regulates the development of vitiligo remains unclear. In the present study, naïve T and CD8+ T cells were isolated from a patient with non­segmental vitiligo by flow cytometry. The cells were differentiated into Treg cells by treatment with interleukin­2, transforming growth factor­ß and retinoic acid. In addition, miR­155 agonists and antagonists were used to investigate the effect of miR­155 on the proliferation of CD8+ T cells, Treg cells and melanocytes. The results demonstrated that the miR­155 agonist significantly decreased the rate of CD8+ T cell growth, as well as promoted the proliferation of melanocytes by inducing an increase in the percentage of Treg cells. By contrast, the miR­155 antagonist inhibited the proliferation of melanocytes by decreasing the percentage of Treg cells. miR­155 protected melanocyte survival by increasing the number of Treg cells and by decreasing the number of CD8+ T cells. Therefore, these data may provide a new prospect for the treatment of vitiligo.

3.
Drug Des Devel Ther ; 13: 2371-2379, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409971

RESUMO

Background: Cervical cancer is the second most common malignant cancer in women worldwide. Evidence indicated that miR-664 was significantly downregulated in cervical cancer. However, the mechanisms by which miR-664 regulates the tumorigenesis of cervical cancer remain unclear. Thus, this study aimed to investigate the role of miR-664 in cervical cancer. Methods: Quantitative reverse transcription polymerase chain reaction was used to detect the level of miR-664 in tumor tissues and cell line. The dual luciferase reporter system assay and Western blotting were used to explore the interaction of miR-664 and c-Kit in cervical cancer. Results: The expression of miR-664 in patients with cervical cancer was dramatically decreased compared with that in adjacent tissues. MiR-664 mimics significantly inhibited proliferation in SiHa cells via inducing apoptosis. In addition, miR-664 mimics induced apoptosis in SiHa cells via increasing the expressions of Bax and active caspase 3 and decreasing the level of Bcl-2. Moreover, dual-luciferase assay showed that c-Kit was the directly binding target of miR-664 in SiHa cells; overexpression of miR-664 downregulated the expression of c-Kit. Meanwhile, upregulation of miR-664 significantly decreased the levels of c-Myc and Cyclin D in cells. Furthermore, miR-664 markedly inhibited tumor growth of cervical cancer in xenograft. Conclusion: Our data indicated that miR-664 exerted antitumor effects on SiHa cells by directly targeting c-Kit in vitro and in vivo. Therefore, miR-664 might be a potential therapeutic target for the treatment of patients with cervical cancer.

4.
Oncotarget ; 9(90): 36057-36066, 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30546827

RESUMO

Hepatocellular carcinoma (HCC) is the most common neoplasm and is a leading cause of cancer-related death. Despite advances in the diagnosis and management of HCC, its prognosis remain unfavorable. Accumulating evidence has shown that long intergenic noncoding RNAs (lincRNAs) play central roles in the development of HCC. In this study, we identified a long intergenic noncoding RNA referred to as lincRNA P7 in HCC and explored its clinical significance and biological functions in HCC. The expression level of lincRNA P7 was significantly aberrantly deceased in HCC cancer tissues and cells lines. Gain- and loss-of-function experiments revealed that overexpression of lincRNA P7 significantly inhibited the proliferation of HCC-derived cancer cells, whereas lincRNA P7 knockdown promoted cell growth. Mechanistically, lincRNA P7 blocked Erk1/2 signaling and repressed activation of the STAT1 pathway. In nude mouse models, we show that overexpression of lincRNA P7 effectively repressed HCC xenograft tumor growth in vivo. Moreover, a clinical investigation demonstrated that down-regulated lincRNA P7 expression correlated with liver cirrhosis, Hepatitis B virus (HBV) infection, clinical stage of the tumor and recurrence. A Kaplan-Meier survival analysis showed that the expression of lincRNA P7 was significantly related to overall survival (P = 0.003) and recurrence-free survival (P = 0.031). Collectively, our findings suggested that the down-regulation of lincRNA P7 predicts poor clinical outcomes for HCC patients and might be a powerful candidate prognostic biomarker and target in HCC.

5.
Indian J Dermatol Venereol Leprol ; 84(3): 269-274, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29491190

RESUMO

Background: Vitiligo is a disorder caused by the loss of the melanocyte activity on melanin pigment generation. Studies show that oxidative-stress induced apoptosis in melanocytes is closely related to the pathogenesis of vitiligo. Glutamine is a well known antioxidant with anti-apoptotic effects, and is used in a variety of diseases. However, it is unclear whether glutamine has an antioxidant or anti-apoptotic effect on melanocytes. Aims: The aim of this study was to investigate the protective effects of glutamine on a human melanocyte oxidative stress model. Methods: The oxidative stress model was established on human melanocytes using hydrogen peroxide. The morphology and viability of melanocytes, levels of oxidants [reactive oxygen species and malondialdehyde], levels of antioxidants [superoxide dismutase and glutathione-S-transferase], and apoptosis-related indicators (caspase-3, bax and bcl-2) were examined after glutamine exposure at various concentrations. Expressions of nuclear factor-E2-related factor 2, heme oxygenase-1, and heat shock protein 70 were detected using western blot technique after glutamine exposure at various concentrations. Results: Our results demonstrate that pre-treatment and post-treatment with glutamine promoted melanocyte viability, increased levels of superoxide dismutase, glutathione-S-transferase and bcl-2, decreased levels of reactive oxygen species, malondialdehyde, bax and caspase-3, and enhanced nuclear factor-E2-related factor 2, heme oxygenase-1, and heat shock protein 70 expression in a dose dependent manner. The effect of pre-treatment was more significant than post-treatment, at the same concentration. Limitations: The mechanisms of glutamine activated nuclear factor-E2-related factor 2 antioxidant responsive element signaling pathway need further investigation. Conclusions: Glutamine enhances the antioxidant and anti-apoptotic capabilities of melanocytes and protects them against oxidative stress.


Assuntos
Antioxidantes/farmacologia , Glutamina/farmacologia , Melanócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Adolescente , Adulto , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Glutamina/uso terapêutico , Humanos , Peróxido de Hidrogênio/toxicidade , Masculino , Melanócitos/metabolismo , Estresse Oxidativo/fisiologia , Vitiligo/tratamento farmacológico , Vitiligo/metabolismo , Adulto Jovem
6.
Antiviral Res ; 153: 78-84, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29501624

RESUMO

Human adenoviruses (HAdVs) are prevalent in pediatric and adult patients with severe acute respiratory disease (ARD). To date, there have been no widely used HAdV vaccines available. In this report, we developed a cold-adapted attenuated influenza virus, termed rg HAdV-Flu ca, carrying epitopes from HAdV hexon protein in the backbone of the ca influenza vaccine neuraminidase (NA) gene using reverse genetics. Rg HAdV-Flu ca virus exhibited a cold-adapted (ca) phenotype, and its morphological characteristics were observed using electron microscopy. Moreover, BALB/c mice were immunized intranasally (i.n.) with 105, 106 or 107 TCID50 rg HAdV-Flu ca. Results showed a specific, robust antibody response against influenza and HAdV in a dose-dependent manner. More importantly, potent humoral, mucosal and cellular immune responses protected against subsequent wild-type HAdV-3 or HAdV-7 challenges, as determined by a significant decrease in viral titers and a noticeable alleviation of histopathological alterations in the lung tissue of challenged mice. These findings demonstrate that rg HAdV-Flu ca warrants attention as a potential vaccine candidate against HAdV infection.


Assuntos
Adenovírus Humanos/imunologia , Vacinas contra Influenza/imunologia , Orthomyxoviridae/imunologia , Infecções por Adenoviridae/prevenção & controle , Adenovírus Humanos/genética , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Epitopos/genética , Epitopos/imunologia , Imunidade Celular , Imunidade nas Mucosas , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Vacinas contra Influenza/isolamento & purificação , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/prevenção & controle , Genética Reversa , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/isolamento & purificação , Vírion/ultraestrutura , Viroses
7.
J Mol Cell Biol ; 10(6): 573-585, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29121325

RESUMO

Influenza virus (IAV) infection is a major cause of severe respiratory illness that affects almost every country in the world. IAV infections result in respiratory illness and even acute lung injury and death, but the underlying mechanisms responsible for IAV pathogenesis have not yet been fully elucidated. In this study, the basic fibroblast growth factor 2 (FGF2) level was markedly increased in H1N1 virus-infected humans and mice. FGF2, which is predominately derived from epithelial cells, recruits and activates neutrophils via the FGFR2-PI3K-AKT-NFκB signaling pathway. FGF2 depletion or knockout exacerbated influenza-associated disease by impairing neutrophil recruitment and activation. More importantly, administration of the recombinant FGF2 protein significantly alleviated the severity of IAV-induced lung injury and promoted the survival of IAV-infected mice. Based on the results from experiments in which neutrophils were depleted and adoptively transferred, FGF2 protected mice against IAV infection by recruiting neutrophils. Thus, FGF2 plays a critical role in preventing IAV-induced lung injury, and FGF2 is a promising potential therapeutic target during IAV infection.


Assuntos
Lesão Pulmonar Aguda/virologia , Fator 2 de Crescimento de Fibroblastos/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/imunologia , Infiltração de Neutrófilos , Infecções por Orthomyxoviridae/imunologia , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/imunologia , Animais , Feminino , Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Humanos , Influenza Humana/complicações , Influenza Humana/terapia , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/complicações , Infecções por Orthomyxoviridae/terapia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico
8.
Medicine (Baltimore) ; 96(49): e8391, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29245213

RESUMO

RATIONAL: Nodular cutaneous lupus mucinosis is regarded as a distinctive cutaneous mucinosis deposition with systemic lupus erythematosus(SLE). All typical cases occurred as asymptomatic cutaneous papules, nodules, or plaques on the trunk, upper and lower extremities, and face. Histopathology is mainly revealed abundant mucin deposits among splayed collagen bundles in the dermis. At the same time we can find A the typical clinical manifestations and biological evidence of SLE. Here, we report the first case of nodular cutaneous lupus mucinosis that did not present with any prior symptoms or history of SLE. PATIENT CONCERNS: We report the first case of nodular cutaneous lupus mucinosis that did not present with any prior symptoms or history of SLE. The patient was 34 years old. One year before admission, nodules began to appear on the elbows, chest, and back, and 2 months before admission erythema occurred on the face. Other notable clinical symptoms were not observed and had no prior history of SLE. DIAGNOSES: Initially, this patient was misdiagnosed by other clinics as having eczema. After histopathological assessment of skin biopsy and examination of antinuclear antibody signals, the patient was correctly diagnosed with nodular cutaneous lupus mucinosis. INTERVENTIONS: Followed administration of systemic steroids and hydroxychloroquine. OUTCOMES: the eruptions quickly disappeared and laboratory indicators improved. LESSONS: This case highlights the need for diagnostic vigilance in cases involving papules and nodules initially developing on the chest and elbows in the absence of obvious lupoid symptoms. We recommend a lower threshold for performing histopathological analysis and examination of antinuclear antibody signals in view of the rare but serious possibility of nodular cutaneous lupus mucinosis.


Assuntos
Lúpus Eritematoso Cutâneo/complicações , Mucinoses/etiologia , Adulto , Humanos , Masculino
9.
Front Microbiol ; 8: 2187, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29163456

RESUMO

Fibroblast growth factor 2 (FGF2 or basic FGF) regulates a wide range of cell biological functions including proliferation, angiogenesis, migration, differentiation, and injury repair. However, the roles of FGF2 and the underlying mechanisms of action in influenza A virus (IAV)-induced lung injury remain largely unexplored. In this study, we report that microRNA-194-5p (miR-194) expression is significantly decreased in A549 alveolar epithelial cells (AECs) following infection with IAV/Beijing/501/2009 (BJ501). We found that miR-194 can directly target FGF2, a novel antiviral regulator, to suppress FGF2 expression at the mRNA and protein levels. Overexpression of miR-194 facilitated IAV replication by negatively regulating type I interferon (IFN) production, whereas reintroduction of FGF2 abrogated the miR-194-induced effects on IAV replication. Conversely, inhibition of miR-194 alleviated IAV-induced lung injury by promoting type I IFN antiviral activities in vivo. Importantly, FGF2 activated the retinoic acid-inducible gene I signaling pathway, whereas miR-194 suppressed the phosphorylation of tank binding kinase 1 and IFN regulatory factor 3. Our findings suggest that the miR-194-FGF2 axis plays a vital role in IAV-induced lung injury, and miR-194 antagonism might be a potential therapeutic target during IAV infection.

10.
J Investig Med ; 65(7): 1084-1088, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28790132

RESUMO

Psoriasis is a chronic skin disease characterized by abnormal keratinocyte proliferation and differentiation, inflammation, and angiogenesis. Overexpression of tribbles homolog3 (TRB3), which belongs to the tribbles family of pseudokinases, has been found in several human tumors and metabolic diseases, but its role in psoriasis has not been fully clarified. The aim of this study is to investigate the expression of TRB3 in psoriasis and explore its roles in the proliferation of keratinocytes. Twenty-four patients with psoriasis vulgaris were recruited for the study. Diagnosis of psoriasis was based on clinical and histologic examinations. Immunohistochemistry and real-time reverse transcription PCR (RT-PCR) were performed to determine protein and messenger RNA (mRNA) expression of TRB3 in psoriasis lesions. 5-Bromo-2-deoxyUridine (BrdU) incorporation assay were performed for cell proliferation. Cell cycle distribution was assessed by flow cytometry analysis. The levels of TRB3 is elevated in psoriatic lesions compared with psoriatic non-lesions. The HaCat cells expressed the TRB3 gene. We found TRB3 silencing to significantly inhibit HaCat cell proliferation. Furthermore, the specific knockdown of TRB3 slowed down the cell cycle at the gap 0/first gap phase. In conclusion, our data suggest that TRB3 is overexpressed in lesions of patients with psoriasis and may be involved in the abnormal proliferation of keratinocytes. Therefore, TRB3 may be a potential therapeutic target for psoriasis.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Queratinócitos/metabolismo , Queratinócitos/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Psoríase/genética , Psoríase/patologia , Proteínas Repressoras/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular , Proliferação de Células , Regulação para Baixo/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/genética , Adulto Jovem
12.
Front Microbiol ; 8: 587, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28421067

RESUMO

An avian-origin influenza A (H7N9) virus was a cause for concern in China in the spring of 2013. Most H7N9 infections resulted in acute respiratory distress syndrome (ARDS), which is a severe form of acute lung injury (ALI) that contributes to morbidity and mortality. In this study, we induced viral ALI by infecting wild-type and CCL2-deficient mice with influenza H7N9 virus. The results suggested a close association between C-C motif chemokine ligand 2 (CCL2) expressions and ALI induced by a lethal H7N9 virus strain (A/Hebei/01/2013). Elevated CCL2 levels were also detected in confirmed human cases of H7N9 and the bronchoalveolar lavage fluid (BALF) of H7N9-infected mice. Moreover, CCL2 was overexpressed in the lung tissue of infected mice. More importantly, CCL2 deficiency ameliorated H7N9-induced ALI in mice as determined by weight loss, survival rate, the wet:dry ratio of the lung, and pathology. Taken together, our findings demonstrate that CCL2 is essential for H7N9 virus infection and thus that it is a potential therapeutic target for influenza.

13.
Appl Opt ; 56(3): 380-384, 2017 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-28157889

RESUMO

We present a dual-view liquid crystal display that allows two faces of the display to be viewed in opposite directions to show different image/video content simultaneously. This device is characterized by a two-domain twisted nematic liquid crystal and a patterned E-type polarizer. Its key optical performance, including the voltage-luminance curve, crosstalk, and viewing angle, has been investigated. When observed at the best viewing angle, the crosstalk between the right and left views is less than 0.07% for all grayscales. In addition, this type of crosstalk can be immune to the misalignment between the polarizers and the liquid crystal layer. For each right/left view, the range of the viewing angle spans roughly 50°.

14.
Opt Express ; 25(3): 2130-2142, 2017 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29519061

RESUMO

We propose a see-through near-eye display, which is dedicated to the visually impaired users who suffer from refractive anomalies. Our solution is characterized by a pair of corrective lenses coated with multiplexed volume holograms. Its key performance including diffraction efficiency, field of view, modulation transfer function, and distortion has been studied.


Assuntos
Óculos , Óptica e Fotônica , Erros de Refração/terapia , Desenho de Equipamento , Humanos , Erros de Refração/fisiopatologia
15.
Acta Biochim Biophys Sin (Shanghai) ; 49(1): 74-82, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27974288

RESUMO

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory infection in infants and children, but there is still no licensed vaccine available. In this report, we developed virus-like particle (VLP) vaccines based on the Bac-to-Bac baculovirus expression system, consisting of an influenza virus matrix (M1) protein and the RSV fusion protein (F) or glycoprotein (G). These RSV VLPs were identified by western blot analysis and electron microscopy. Female BALB/c mice immunized intranasally (i.n.) with RSV-F VLPs, RSV-G VLPs, or both showed viral-specific antibody responses against RSV. Total IgG, IgG1, IgG2a, and mucosal IgA were detected in mice with RSV-F plus RSV-G VLPs, revealing potent cellular and mucosal immune responses. Moreover, we found that these mixed RSV VLPs conferred enhanced protection against live RSV challenges, showing significant decreases in lung viral replication and obvious attenuation of histopathological changes associated with viral infections. These results demonstrate that RSV-F plus RSV-G VLPs by intranasal vaccination is a promising vaccine candidate that warrants further evaluation using cotton rat and primate models.


Assuntos
Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Administração Intranasal , Animais , Feminino , Imunidade Celular , Imunidade nas Mucosas , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Vírus Respiratório Sincicial/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia
16.
Immunobiology ; 221(12): 1378-1381, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27502164

RESUMO

Vitiligo is a common established depigmentation skin disease characterized by the presence of activated T lymphocytes anti melanocytes within the skin. T-cell immunity mainly mediates the destruction of melanocytes and is one of the main mechanisms involved in the pathogenesis of non-segmental vitiligo. Our previous study had identified several differentially expressed miRNAs and found that the expression of miR-3940-5p was downregulated in vitiligo patients. According to the research findings, we hypothesized that the novel miRNA plays a potential role on human cutaneous T lymphocytes in the action mechanism of immune imbalance in vitiligo.


Assuntos
Subunidade gama Comum de Receptores de Interleucina/genética , Melanócitos/imunologia , MicroRNAs/genética , Pele/patologia , Linfócitos T/imunologia , Vitiligo/imunologia , Linhagem Celular , Simulação por Computador , Bases de Dados Genéticas , Regulação para Baixo , Regulação da Expressão Gênica , Humanos , Subunidade gama Comum de Receptores de Interleucina/metabolismo , Ativação Linfocitária , Transdução de Sinais
18.
Sci Rep ; 6: 19840, 2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26813885

RESUMO

Respiratory syncytial virus (RSV) infection is a major cause of severe lower respiratory illness in infants and young children, but the underlying mechanisms responsible for viral pathogenesis have not been fully elucidated. To date, no drugs or vaccines have been employed to improve clinical outcomes for RSV-infected patients. In this paper, we report that angiotensin-converting enzyme-2 (ACE2) protected against severe lung injury induced by RSV infection in an experimental mouse model and in pediatric patients. Moreover, ACE2 deficiency aggravated RSV-associated disease pathogenesis, mainly by its action on the angiotensin II type 1 receptor (AT1R). Furthermore, administration of a recombinant ACE2 protein alleviated the severity of RSV-induced lung injury. These findings demonstrate that ACE2 plays a critical role in preventing RSV-induced lung injury, and suggest that ACE2 is a promising potential therapeutic target in the management of RSV-induced lung disease.


Assuntos
Lesão Pulmonar/metabolismo , Peptidil Dipeptidase A/metabolismo , Infecções por Vírus Respiratório Sincicial/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Modelos Animais de Doenças , Lesão Pulmonar/genética , Lesão Pulmonar/patologia , Lesão Pulmonar/virologia , Camundongos , Camundongos Knockout , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/farmacologia , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Sistema Renina-Angiotensina , Infecções por Vírus Respiratório Sincicial/genética , Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/virologia , Índice de Gravidade de Doença
20.
PLoS One ; 10(4): e0124651, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25909503

RESUMO

Influenza A virus causes annual epidemics and occasional pandemics in humans. Here, we investigated four members of the fibroblast growth factor receptor (FGFR) family; FGFR1 to 4, and examined their expression patterns in human lung epithelial cells A549 with influenza A virus infection. We identified a functional role of FGFR1 in influenza A/Puerto Rico/8/1934 (PR8) and A/Anhui/01/2005 (H5N1) virus replication. Our results showed that FGFR1 silencing by siRNA interference promoted influenza A/PR8 and H5N1 virus replication in A549 cells, while lentivirus-mediated exogenous FGFR1 expression significantly suppressed influenza A virus replication; however, FGFR4 did not have the same effects. Moreover, FGFR1 phosphorylation levels were downregulated in A549 cells by influenza A virus infection, while the repression of FGFR1 kinase using PD173074, a potent and selective FGFR1 inhibitor, could enhance virus replication. Furthermore, we found that FGFR1 inhibits influenza virus internalization, but not binding, during viral entry. These results suggested that FGFR1 specifically antagonizes influenza A virus replication, probably by blocking viral entry.


Assuntos
Vírus da Influenza A/fisiologia , Influenza Humana/metabolismo , Influenza Humana/virologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Replicação Viral , Linhagem Celular , Receptores ErbB/efeitos dos fármacos , Receptores ErbB/genética , Expressão Gênica , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/genética , Pirimidinas/farmacologia , Interferência de RNA , RNA Interferente Pequeno/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Transcriptoma , Transdução Genética , Ligação Viral , Internalização do Vírus , Replicação Viral/efeitos dos fármacos
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