ABSTRACT
Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of Pycnogenol® (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth factor-β1 (TGF-β1) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in TGF-β1/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.
Subject(s)
Animals , Humans , Mice , Bronchoalveolar Lavage Fluid , Collagen , Inflammation , Lung , Lung Diseases, Obstructive , Phosphorylation , Pulmonary Disease, Chronic Obstructive , Pulmonary Fibrosis , Smoke , Tobacco ProductsABSTRACT
OBJECTIVE:To study the effects of Astragalus granules on the expression of Caveolin-3(Cav-3)and Smad family member 3 (Smad3) in the myocardial cells of rats with viral myocarditis. METHODS:90 rats were randomly divided into a nor-mal group,a model group,a Shenmai injection group [positive drug,0.2 g/(kg·d)] and the groups of low,medium and high-dose Astragalus granules [0.42,0.84,1.68 g/(kg·d)],with 15 rats in each group. The rats in all groups except for the normal group were given CVB3 ip for the establishment of viral myocarditis model. Meanwhile,the rats in the drug administration groups were given corresponding drugs ig,while those in the normal group and the model group were given normal saline ig,for 15 consecu-tive days. 5 rats were selected from each group respectively on the 3rd,9th and 15th days of drug use to take an experiment. For the rats,the pathological change of the cardiac muscle tissue was observed and scored,and the mRNA and protein expression of Cav-3 and Smad3 in the myocardial cells were detected. RESULTS:After 15 days of drug use,compared to the normal group,the rats of the model group had hyperplasia of a large number of cardiac muscle fibers,obvious lesions at cardiac muscle fibers, and significantly higher pathological score and levels of the mRNA and protein expression of Cav-3 and Smad3 in the myocardial cells (P<0.05). Compared to the model group,the rats in the drug administration groups had cardiac muscle tissue lesions improved and had obviously lower pathological score and levels of the mRNA and protein expression of Cav-3 and Smad3 in the myocardial cells(P<0.05). CONCLUSIONS:Astragalus granules can markedly downregulate the gene expression of Cav-3 and Smad3 in the myocardial cells of rats with viral myocarditis,which is inferred as a prevention and treatment mechanism of viral myocarditis.
ABSTRACT
One of the major signaling pathways that determine the tumor aggression and patient outcome in pancreatic cancer is the transforming growth factor-beta (TGF-ß) pathway. It is inactivated at various levels in pancreatic cancer and plays a dual role in tumor initiation and progression. The Smad family of proteins transduce signals from the TGF-ß superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. This review discusses the structure, function and regulation of various participating Smad family members, and their individual roles in determining the progression and outcome of pancreatic cancer patients, with a special emphasis on Smad4.
Subject(s)
Cell Differentiation , Cell Proliferation , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Phosphorylation , Receptors, Transforming Growth Factor beta/genetics , Receptors, Transforming Growth Factor beta/metabolism , Signal Transduction , Smad4 Protein/chemistry , Smad4 Protein/genetics , Smad4 Protein/metabolism , Smad6 Protein/genetics , Smad6 Protein/metabolism , Smad7 Protein/genetics , Smad7 Protein/metabolism , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolismABSTRACT
OBJECTIVE: To observe the regulatory effect of SNMC on the gene expression of the Smad family in pulmonary fibrosis model rats.METHODS: A total of 174 rats were assigned to 6 groups: normal group,model group,positive prednisolone acetate group,SNMC(20,15,10 mL?kg-1?d-1) groups,with the latter 5 groups treated with bleomycin injection to induce pulmonary fibrosis model.At 24 h after modeling,the rats in 6 groups were treated with corresponding drugs day by day before being sacrificed at 1,12,28 days after first-time treatment for extracting of RNA from pulmonary tissues.The expression levels of Smad3,Smad4 and Smad7 were assayed by RT-PCR respectively.RESULTS: As compared with model group,the expression levels of Smad4 and Smad7 genes were down-regulated but the expression level of Smad3 gene was up-regulated in SNMC groups,whereas the expression levels of 3 kinds of genes were all down-regulated in positive prednisolone acetate group.CONCLUSION: SNMC is more effective than prednisolone acetate in reversing the abnormal expression of Smad family in pulmonary fibrosis model rats.