RESUMO
Cartilage oligomeric matrix protein (COMP) regulates transforming growth factor-ß (TGF-ß) signaling pathway, which has been proved to be associated with skin fibrosis and pulmonary fibrosis. Atrial fibrosis is a major factor of atrial fibrillation (AF). Nevertheless, the interaction between COMP and TGF-ß as well as their role in AF remains undefined. The purpose of this study is to clarify the role of COMP in AF and explore its potential mechanism. The hub gene of AF was identified from two datasets using bioinformatics. Furthermore, it was verified by the downregulation of COMP in angiotensin-II (Ang-II)-induced AF in mice. Moreover, the effect on AF was examined using CCK8 assay, ELISA, and western blot. The involvement of TGF-ß pathway was further discussed. The expression of COMP was the most significant among all these hub genes. Our experimental results revealed that the protein levels of TGF-ß1, phosphorylated Smad2 (P-Smad2), and phosphorylated Smad3 (P-Smad3) were decreased after silencing COMP, which indicated that COMP knockdown could inhibit the activation of TGF-ß pathway in AF cells. However, the phenomenon was reversed when the activator SRI was added. COMP acts as a major factor and can improve Ang-II-induced AF via TGF-ß signaling pathway. Thus, our research enriches the understanding of the interaction between COMP and TGF-ß in AF, and provides reference for the pathogenesis and diagnosis of AF.
Assuntos
Fibrilação Atrial , Animais , Camundongos , Angiotensina II/metabolismo , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/genética , Proteína de Matriz Oligomérica de Cartilagem , Fibrose , Transdução de Sinais , Fator de Crescimento Transformador beta , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase receptor implicated in tumourigenesis that may be an attractive target for anti-cancer treatment. In this study, the expression and clinical significance of IGF1R were investigated in serum and lung cancer tissues from small cell lung cancinoma (SCLC). We also compared the effect of IGF1R up-regulation and IGF1R inhibition on viability and apoptosis of NCI-H446 cells. We found the concentration of IGF1R in blood serum was significantly increased and positive IGF1R protein in cancer tissue was more prevalent in SCLC. A statistically significant correlation among IGF1R-positve tumors, lymph node metastasis and local invasion was discussed. Furthermore, IGF1R overexpression lead to an increase of cell survival and suppressed cell apoptosis, IGF1R silencing mediated by RNAi abrogate this response of NCI-H446 cells. Our results further demonstrated that the effects of these treatments may be assigned to the effective inhibition of lung cancer cells from Akt/P27(Kip1) pathway in IGF-1R signaling. These features may have important implications for future anti-IGF1R therapeutic approaches.
Assuntos
Proliferação de Células/genética , Neoplasias Pulmonares/patologia , Receptores de Somatomedina/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Apoptose/genética , Proteínas de Ciclo Celular/biossíntese , Linhagem Celular Tumoral , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Interferência de RNA , RNA Interferente Pequeno/genética , Receptor IGF Tipo 1 , Receptores de Somatomedina/sangue , Receptores de Somatomedina/genética , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológicoRESUMO
OBJECTIVE: To study how blood supply of the esophageal and gastric stumps influences the anastomotic healing after esophagogastrostomy in rabbits. METHODS: Twenty-seven New Zealand rabbits were randomly divided into 3 groups to receive esophagogastrostomy, followed by different procedures. Except for those in group I, all the rabbits were subjected to procedures of reducing the blood supply either of the esophageal or the gastric stump (group II and group III, respectively), followed by single-layer esophagogastric anastomoses using interrupted 5-0 polypropylene sutures. Ten days after operation, all the rats were killed and the anastomotic sites excised for measurement of the inner diameter, tensile strength, and hydroxyproline concentration. RESULTS: Healing of the esophagograstric anastomosis was obtained in all the rabbits but one with anastomotic leakage in group I and one with perforation of the gastric fundus in group III. The anastomotic inner diameters were similar in all the three groups, whereas the tensile strength and hydroxyproline concentration at the anastomoses decreased in group III in comparison with the other two groups (P<0.05) that had similar measurements (P>0.05). CONCLUSIONS: Extended length of the free esophageal stump does not significantly affect anastomotic healing as decrease of blood supply in the gastric stump.
