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@#Periodontitis is the inflammation of periodontal tissue caused by dental plaque, which absorbs the alveolar bone and cementum. The immune response triggered by CD4+T cells is the key factor for the aggravation of periodontitis. The activation of dendritic cells and the receptor activator of the NF-κB ligand (RANKL) pathway is an important link in the alveolar bone resorption of periodontal tissue. Pro-inflammatory factors such as interferon-γ (IFN-γ), tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) also play important roles in the development of periodontitis. Interleukin-37(IL-37), which is a newly discovered cytokine in the IL-1 family, has five shear variants from a to e, among which the clover β-structure encoded by exon 4 plays an important role in the binding of cytokines and the corresponding receptors. IL-37 has strong anti-inflammatory and inhibition of autoimmunity, can enter the nucleus with the help of caspase-1 and bind with Smad proteins to regulate the transcription of pro-inflammatory genes. Extracellular IL-37 can bind to IL-18 binding protein and inhibit the production of pro-inflammatory factors. IL-37 can inhibit the progression of periodontitis by inhibiting the RANKL signaling pathway, inhibiting the proliferation and differentiation of dendritic cells and CD4+T cells, binding to Smad proteins, and releasing pro-inflammatory factors such as IFN-γ and TNF-α. The IL-37 concentration in periodontal tissue can indicate the progression of periodontitis. Few studies have described the interaction between the anti-inflammatory factor IL-37 and periodontitis. Thus, in this paper, the structure and function of IL-37 and the related factors between IL-37 and periodontitis will be reviewed.
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Objective: To observe the effects of transforming growth factor-β1 (TGF-β1) and atorvastatin on expressions of collagen type I P-Smad2, Smad4 and Smad7 in human atrial ifbroblasts, and to explore the ifbrosis and anti-ifbrosis mechanisms in human atrium. Methods: Human right atrial appendage tissue was obtained from the cardiac surgery in our hospital and the atrial ifbroblasts were isolated and cultured by generations. The effects of TGF-β1 and atorvastatin on atrial ifbroblast proliferation was detected by MTT method and the effect of TGF-β1 at (0, 0.1, 1.0, 5.0, 10.0, 20.0, 50.0) ng/ml and atorvastatin at (0, 0.1, 1.0, 10.0, 100.0) μmol/L on mRNA and protein expressions of collagen type I P-Smad2, Smad4 and Smad7 in atrial ifbroblasts were examined by RT-PCR and Western-blotting analysis respectively. Results: MTT detection presented that compared to TGF-β1 at 0 ng/ml, with the intervention of TGF-β1 at (1 and 10) ng/ml, the mRNA and protein expressions of collagen type I P-Smad2, Smad4 increased,P<0.05 and the expressions of Smad7 decreased,P<0.05. Compared to TGF-β1 at 10.0 ng/ml, with the intervention of TGF-β1 + atorvastatin at 10.0 μmol/L or with atorvastatin at 10.0 μmol/L alone, the mRNA and protein expressions of collagen type I P-Smad2, Smad4 decreased,P<0.05and expressions of Smad7 increased,P<0.05. Conclusion: TGF-β1 promotes human atrial ifbroblast proliferation and collagen type I expression, while atorvastatin inhibits such proliferation and expression, the effect might be done by affecting TGF-β1/Smads pathway in human atrial ifbroblasts.
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Objective To study the regulating effect of complementing calcium and invigorating kidney method on the bone morphogenetic protein-4(BMP-4) and signal transduction mechanism.Methods Female Wistar rats were randomly divided into seven groups:normal group,model group,low-,middle-,high-dose yster calcium compound Chinese medicine for reinforcing kidney group,Gushukang granule group,oyster shell calcium tablets group.The model of postmenopausal osteoporosis was established through ovariectomy in rats.The osteoporosis rats were treated with nanometer calcium and invigorating kidney Chinese medicine Gushukang granule,and oyster shell carbonate chewable tablets were used as positive-control groups,the normal rats as standard control,and the model rats as model control.After 12 weeks of the treatment,the indexes were tested.The bone mineral density(BMD) of femoral bone in vitro was detected by dual-energy X-ray densitometer and the expression of BMP-4 and Smad 5,6 mRNA were detected by reverse transcription-polymerase chain reation(RT-PCR).Results Compared with the model rats,BMD of femoral bone in Chinese medicine groups(high dose,middle dose,low dose) increased obviously(P
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Objective To examine the expression of TGF-?1/Smads signaling pathway in renal tubulointerstitial fibrosis.Methods Male SD rats were divided into control,sham operation and tubulointerstitial fibrosis groups.They were sacrificed at day 3,7,14,28 after operation.Use masson coloration to examine the area of pathological changes.The level of TGF?1,p-Smad2/3 and smad7 protein was examined by immunohistochemistry staining and Western blot.The level of TGF-?1 mRNA and smad7 mRNA was analyzed by RTPCR.Results Compared with sham operation group,TGF-?1 and p-Smad2/3 were significantly increased in UUO rats,while smad7 protein reduced in it.The mRNA of TGF-?1 and smad 7 increased from day 3 to day 28.Smads protein plays an important role in the synthesis and accumulation of extracellular matrix in tubulointerstitial area.The reduction of smad 7 protein may be a major cause of the interstitial fibrosis in this model.Conclusion TGF-? /Smads protein pathway perhaps is essential in the development of tubulointerstitial fibrosis.
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Transforming growth factor-?(TGF-?) is a kind of multifunctional cytokine that regulates cell growth,differentiation,cellular senescence,apoptosis,wound healing and embryo development.As a tumor suppressor,deregulated or aberrant TGF-? signaling has been strongly implicated in human solid tumors,as well as in normal and malignant hematopoiesis.TGF? exerts an inhibitory role during the whole procedure of hematopoiesis.As a cell cycle inhibitor,it maintains cells in a quiescent state and can downregulate expression of hematopoiesis activators and oncoproteins.In malignant hematopoiesis,altered expression of coactivators or corepressors involve in TGF-?-induced transcriptional responses and loss/disruption of TGF-? target gene expression.Then malignant cells grow and differentiate abnormally.In acute promyelocytic leukemia,PML-RAR? may inhibit TGF-? signaling through inhibition of cPML and nPML.Degradation of PML-RAR? by ATRA restores this signaling pathway.
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Objective To investigate the effect and mechanism of Artemisia Argyi extracting solution on anti-hepatic fibrosis.Methods Twenty-four experimental Wistar rats were randomized into four groups:Artemisia group,Danshen group,physiological saline group,and blank control group,with 6 in each.The Artemisia group was treated with 20% Artemisia Argyi extracting solution,the Danshen group with Danshen (salvia) solution,and the physiological saline group with physiological saline by gavage,20ml/kg.After treating three times per day for 3 days,sera were obtained and made a mixture with DMEM to be volume fraction as 5%,10%,and 20%.Effect of different volume fraction of extracting solution on TGF-?1 Smad3 and Smad7 mRNA and protein were detected.Results After treating with 5%,10% and 20% Artemisia Argyi extracting solution contained rat serum for 24h,contrasted to the black control group,the expression of TGF-?1 mRNA level was (0.82?0.03),(0.72?0.03) and (0.67?0.04) times,and the expression of TGF-?1 protein was (0.66?0.09),(0.34?0.05) and (0.31?0.07) times respectively;contrasted to the physiological saline group,the expressions of TGF-?1 mRNA and protein were significantly decreased (P
ABSTRACT
Transforming growth factor-? (TGF-?) is a multifunctional peptide growth factor with a wide range of effects. TGF-? signals are conveyed through cell-surface serine/threonine kinase receptors to the downstream cytoplasmic mediators, known as Smads proteins. Receptor-regulated Smads become phosphorylated by activated type Ⅰ receptors and form heteromeric complexes with a common Smad-Smad4, which translocates into the nucleus to regulate gene transcription. Inhibitory Smads inhibit the activation of receptor-regulated Smads. There are positive, negative and feedback regulations in the Smads mediated TGF-? signaling pathway.