共查询到10条相似文献,搜索用时 156 毫秒
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《The Journal of asthma》2013,50(5):439-448
Objective. To investigate the role and underlying mechanisms of store-operated Ca2+ entry (SOCE) in mediating the promoting effect of transforming growth factor (TGF)-β1 on the proliferation of airway smooth muscle cells (ASMCs). Methods. Rat bronchial smooth muscle cells were cultured as we described previously. The intracellular Ca2+ concentration ([Ca2+]i) of ASMCs was measured by laser confocal microscope Ca2+ fluorescence imaging with Fluo-3/AM. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and p27 expression assay were used to determine the proliferation rate of ASMCs. Results. We demonstrated that TGF-β1 (10 ng/ml) increased basal (Ca2+]i) level, [Ca2+]i rise induced by thapsigargin-induced Ca2+ release and SOCE in rat ASMCs. This effect of TGF-β1 on SOCE was not inhibited by glucocorticoid dexamethasone (DXM, 100 nM), antioxidant α-tocopherol (100 μM), and intermediate-conductance Ca2+-activated K+ channels (IKCa) inhibitor charybdotoxin (100 nM), suggesting that reactive oxygen species and IKCa channels might not mediate the effect of TGF-β1. TGF-β1 slightly increased the expression of Orai1 and STIM1, two important molecules involved in the molecule component and regulation of SOC channels, in the presence of 10% fetal bovine serum (FBS). The proliferation of ASMC stimulated with 2.5% FBS was promoted by TGF-β1, and partly inhibited by non-specific Ca2+ channel blocker SKF-96365 (10 μM) and Ni2+ (100 μM). DXM, α-tocopherol, and charybdotoxin had no effect on the proliferation promoted by TGF-β1. Conclusion. TGF-β1 promotes ASMC proliferation partly through increasing the expression and activity of SOC channels. 相似文献
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Zhi-Wei Yu Ya-Qin Xu Xiao-Juan Zhang Jian-Rong Pan Hong-Xia Xiang Xiao-Hong Gu 《The Journal of asthma》2019,56(4):341-349
Objective: Airway remodeling is an important pathological feature of asthma. Excessive deposition of extracellular matrix (e.g., collagen) secreted from fibroblasts is a major factor contributing to airway remodeling. Currently, the mechanism by which collagen continues to be oversynthesized in the airway remains unclear. In this study, we investigated the role of the microRNA-21 (miR-21) and TGFβ/Smad signaling pathway in human bronchial fibroblasts (HBFs), and explored the regulatory mechanism of airway remodeling. Methods: HBFs were cultured in vitro and treated with the transforming growth factor β (TGFβ), receptor inhibitor (SB431542), and TGFβ1. miR-21 and Smad7 overexpressing lentiviruses, as well as an miR-21 interfering lentivirus were constructed and transfected into HBFs. Western blotting was used to determine the expression of airway remodeling-related proteins and proteins in the TGFβ/Smad signaling pathway. miR-21 expression was measured by quantitative real-time PCR. Results: The high expression of miR-21 induced by TGFβ1 was reduced following the treatment with the SB431542 in HBFs. Smad7 overexpression inhibited the elevated expression of the COL I protein induced by miR-21 overexpression in HBFs. Inhibiting miR-21 expression upregulated the level of Smad7 protein, thus reducing the expression of airway remodeling-related proteins induced by TGFβ1 stimulation in HBFs. Conclusions: TGFβ1 can induce miR-21 expression in HBFs through the TGFβ/Smad signaling pathway to promote airway remodeling. miR-21 downregulates Smad7, activates the TGFβ/Smad signaling pathway, and promotes airway remodeling. Mutual regulation between miR-21 and the TGFβ/Smad signaling pathway in HBFs promotes airway remodeling. 相似文献
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《Digestive and liver disease》2020,52(3):324-330
Liver fibrosis is an important health problem without adequate and effective therapeutics. In this study, effects of thymosinβ4 (Tβ4) on hepatic fibrogenesis and the underlying molecular mechanisms were explored in bile duct ligation (BDL)-induced mice cholestatic liver fibrosis model. Results showed exogenous Tβ4 significantly reduced the mortality and liver/body weight ratio in BDL mice. Histological examinations and biochemical analyses demonstrated that BDL induced evident portal fibrosis and a significant increase in hepatic collagen contents. However, these changes were significantly attenuated by exogenous Tβ4. Quantitative real-time PCR assays showed that Tβ4 suppressed BDL-induced increases in many fibrotic genes expression including α-smooth muscle actin (α-SMA), collagen I, III and fibronectin, TGFβ1, TGFβR II, Smad2, Smad3, and PDGFRβ. Results from immunohistochemistry and Western blots also showed that Tβ4 reduced TGFβ1 and PDGFRβ protein levels in the liver tissues of BDL mice. In vitro studies using LX-2 cells demonstrated that Tβ4 could decrease PDGFRβ and TGFβR II levels in hepatic stellate cells. Taken together, findings in our present studies suggested that exogenous Tβ4 alleviated BDL-induced cholestatic liver fibrosis through downregulating PDGF/PDGFR and TGFβ/Smad pathways. 相似文献
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Qianghua Wu Jianru Wang Renata Skubutyte Christopher K. Kepler Zonggui Huang D. Greg Anderson Irving M. Shapiro Makarand V. Risbud 《Arthritis \u0026amp; Rheumatology》2012,64(10):3324-3333
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To study the regulation of expression of β‐1,3‐glucuronosyltransferase 1 (GlcAT‐1), an important regulator of glycosaminoglycan (GAG) synthesis, by Smad3 in nucleus pulposus (NP) cells.Methods
GlcAT‐1 expression was examined in rat NP and anulus fibrosus (AF) cells treated with transforming growth factor β (TGFβ). The effects of Smad signaling and Smad suppression on GlcAT‐1 were examined in rat NP cells. GlcAT‐1 expression was analyzed in the discs of Smad3‐null mice and in degenerated human NP tissue.Results
TGFβ increased the expression of GlcAT‐1 in rat NP but not rat AF cells. Suppression of GlcAT‐1 promoter activity was evident with dominant‐negative ALK‐5 (DN‐ALK‐5). Cotransfection with Smad3 strongly induced promoter activity independent of TGFβ. Bioinformatics analysis indicated the presence of several Smad binding sites in the promoter; deletion analysis showed that the region between −274 and −123 bp was required for Smad3 response. DN‐Smad3, Smad 3 small interfering RNA, and Smad7 strongly suppressed basal as well as TGFβ‐induced promoter activity. Induction of promoter activity by Smad3 was significantly blocked by DN‐Smad3; Smad7 had a very small effect. Lentiviral transduction of NP cells with short hairpin RNA Smad3 resulted in a decrease in GlcAT‐1 expression and accumulation of GAG. Compared to wild‐type mice, significantly lower expression of GlcAT‐1 was seen in the discs of Smad3‐null mice. Analysis of degenerated human NP tissue specimens showed no positive correlation between GlcAT‐1 and TGFβ expression. Moreover, isolated cells from degenerated human tissue showed a lack of induction of GlcAT‐1 expression following TGFβ treatment, suggesting an altered response.Conclusion
Our findings demonstrate that in healthy NP cells, the TGFβ–Smad3 axis serves as a regulator of GlcAT‐1 expression. However, an altered responsiveness to TGFβ during disc degeneration may compromise GAG synthesis.8.
Jian-Ping Lu Jian-Qun Mao Ming-Sheng Li Shi-Lun Lu Xi-Qi Hu Shi-Neng Zhu Shintaro Nomura 《World journal of gastroenterology : WJG》2003,9(3)
AIM: Initial report on the in situ examination of the mRNA expression of transforming growth factor betas (TGFβs),TGFβ type Ⅱ receptor (TβRII) and telomerase activity in the experimental rat liver tissue during cholangiocarcinogenesis.METHODS: Rat liver cholangiocarcinogenesis was induced by 3'-methyl 4-dimethylazobenzene (3'Me-DAB). In situhybridization was used to examine the TGFβs) and TGFβ type Ⅱ receptor (TβRⅡ) mRNA, in situ TRAP was used to check the telomerase activity in the tissue samples.RESULTS: There was no TGFβs, TβRⅡ mRNA expression or telomerase activity in the control rat cholangiocytes. The expression of TGFβ1, TβRⅡ was increased in regenerative,hyperplastic, dysplastic cholangiocytes and cholangiocarcinoma (CC) cells. The expression of TGFβ2 mRNA was observed in only a part of hyperplastic, dysplastic cholangiocytes. TGFβ3expression was very weak, only in hyperplastic lesion. There was positive telomerase activity in the regenerative,hyperplastic, dysplastic cholangiocytes, and CC cells. Stroma fibroblasts of these lesions also showed positive TGFβs, TβRⅡ mRNA expression and telomerase activity.CONCLUSION: There were TGFβs, TβRⅡ expression and telomerase activity in hyperplastic, dysplastic cholangiocytes,cholangiocarcinoma cells as well as in stroma fibroblasts during cholangiocarcinogenesis. Their expression or activity is important in cholangiocarcinogenesis andstroma formation. 相似文献
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Sonali Sonnylal Christopher P. Denton Bing Zheng Douglas R. Keene Ruming He Henry P. Adams Carolyn S. VanPelt Yong J. Geng Jenny M. Deng Richard R. Behringer Benoit de Crombrugghe 《Arthritis \u0026amp; Rheumatology》2007,56(1):334-344