RESUMO
CONTEXT: Yin Yang-1 (YY-1) is implicated in the pathogenesis of lung cancer which can be complicated with idiopathic pulmonary fibrosis (IPF). OBJECTIVE: The aim of the study was to investigate whether YY-1 is involved in the pathogenesis of IPF and whether represents a common pathogenetic pathway which could explain the coexistence of these disorders. MATERIALS AND METHODS: Lung tissue from 52 patients (37 with IPF and 15 controls) and bronchoalveolar lavage fluid (BALF) from 34 patients (25 with IPF and 9 controls) were studied and YY-1 mRNA expression was evaluated by real-time PCR. RESULTS: YY-1 was expressed in 8% (3/37) of IPF patients and in 6% (1/15) of healthy controls in tissue samples. In addition, 12% (3/25) of IPF patients and 33% (3/9) of healthy controls have expressed YY-1 gene in BALF samples. However, no statistical significant difference in mRNA expression between patients and controls has been detected in both tissue and BAL fluid samples. DISCUSSION AND CONCLUSION: Our results do not support the hypothesis of YY-1 involvement in IPF. However, similar expression of YY-1 gene in two biological samples cannot exclude a possible role of this polymorphic gene in the pathway of IPF. Further studies in a larger scale of patients are needed.
Assuntos
Fibrose Pulmonar Idiopática/metabolismo , Fator de Transcrição YY1/metabolismo , Líquido da Lavagem Broncoalveolar , Estudos de Casos e Controles , Regulação da Expressão Gênica , Humanos , Fator de Transcrição YY1/genéticaRESUMO
PURPOSE OF THE STUDY: Several studies in patients with lung cancer have shown that epidermal growth factor receptor regulates various tumorigenic processes through the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin and Ras/Raf/Mek/Erk (mitogen-activated protein kinase (MAPK)) signalling pathways. The aim of our study is to evaluate whether these pathways are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and to seek indirect evidence of a common pathogenetic pathway with lung cancer. m-RNA expression of oncogenes participating in these two signaling pathways, as well as the combined m-RNA expression of the suppressor genes R-kip and p53 in lung tissue of patients with IPF were evaluated. BASIC PROCEDURES: The study population was composed by two distinct groups. Patients with IPF (n = 25) and control subjects who underwent thoracic surgery for reasons other than interstitial lung disease (n = 10). Expression analysis of the aforementioned oncogenes and suppressor genes was performed using real-time reverse transcription polymerase chain reaction. MAIN FINDINGS: We found no difference in the overall m- RNA expression between controls and IPF in both investigated pathways. However, Braf has been overexpressed in IPF samples (P = 0.01) in contrast with K-ras that has been found downregulated (P < 0.001) in comparison with controls. PRINCIPAL CONCLUSIONS: These findings cannot exclude the hypothesis of involvement of Akt and MAPK signalling pathways in pathogenesis of IPF. However, further investigation is needed in order to verify these data.
Assuntos
Fibrose Pulmonar Idiopática/enzimologia , Fibrose Pulmonar Idiopática/patologia , Pulmão/enzimologia , Pulmão/patologia , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Análise Mutacional de DNA , Demografia , Feminino , Regulação da Expressão Gênica , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Pulmão/fisiopatologia , Sistema de Sinalização das MAP Quinases/genética , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/genética , Proteína de Ligação a Fosfatidiletanolamina/genética , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Espirometria , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismoRESUMO
Increasing evidence implicates angiogenesis in the pathogenesis of fibrotic lung diseases. Distinct angiogenic profiles may, in part, explain differences in immunopathogenesis, clinical course and prognosis. The aim of the study was to seek evidence of involvement of the angiogenic axis Angiopoietin-1 and -2 and their tyrosine kinase receptor, Tie-2 in pathogenesis of idiopathic pulmonary fibrosis (IPF) and interstitial pneumonias associated to collagen tissue disorders (CTD-IPs). We prospectively studied 36 patients with IPF, 23 patients with CTD-IP and 10 healthy subjects. Ang-1, Ang-2 and Tie-2 mRNA expression and protein levels were measured in bronchoalveolar lavage fluid pellets and supernatants, respectively. A statistically significant decrease of Ang-1 protein level has been found in IPF in comparison to controls (p=0.02). We also detected an increased expression of Ang-2 protein in IPF in comparison to CTD-IPs. A significant co-expression was detected between Ang-2 and Tie-2 in protein level (p=0.007) in IPF group. In conclusion, a suppression of the angiogenetic factor Ang-1 was observed at the protein level in IPF which may be important in the pathogenesis of this devastating disease. A differential angiogenetic profile regarding Ang-2 was detected between IPF and CTD-IPs.
Assuntos
Angiopoietina-1/metabolismo , Angiopoietina-2/metabolismo , Fibrose Pulmonar/metabolismo , Receptor TIE-2/metabolismo , Idoso , Angiopoietina-1/genética , Angiopoietina-2/genética , Líquido da Lavagem Broncoalveolar/química , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Doenças do Colágeno/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Fibrose Pulmonar/genética , Receptor TIE-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não ParamétricasRESUMO
BACKGROUND AND AIM: Toll-like receptors (TLRs), a key component of innate immunity, have recently been implicated in the pathogenesis of interstitial lung diseases (ILDs). As the involvement of TLRs has not yet been fully elucidated, the aim of the current study was to examine the expression of various TLRs in the bronchoalveolar lavage fluid (BALF) of patients with ILDs. PATIENTS AND METHODS: We studied prospectively three groups of patients: (1) one group of 35 patients with fibrotic disorders, 16 with idiopathic pulmonary fibrosis (IPF) and 19 with fibrotic interstitial pneumonias associated with collagen tissue disorders (CTD-IPs); (2) one group of 14 patients with pulmonary sarcoidosis; and (3) 11 normal subjects. We evaluated TLR expression with flow cytometry and mRNA expression with real-time PCR. RESULTS: An overexpression of TLR-3 mRNA was found in fibrotic disorders (CTD-IPs/IPF) in comparison with sarcoidosis (mean ± SD, 1.104 ± 1.087 versus 0.038 ± 0.03; P = 0.04). Additionally, TLR-3 mRNA was increased in CTD-IPs in comparison with IPF (P = 0.001), sarcoidosis (P = 0.002) and controls (P = 0.05). An upregulation in TLR-7 and -9 mRNA expression was detected in IPF (P = 0.05) and sarcoidosis (P = 0.05), respectively, when compared to controls. A higher percentage of TLR-9-expressing cells was found in BALF of CTD-IPs when compared to IPF (mean ± SD, 36.7 ± 7.06 versus 14.85 ± 3.82; P = 0.025). CONCLUSION: We observed distinct profiles of TLR expression in fibrotic and granulomatous disorders. It is likely that they could play a key role in the pathogenesis of these diseases and represent future therapeutic targets.