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LAI Ying-yu GAO Xiao-yan ZHOU Hui-shan LI Xin WANG Zhao-yu PENG De-wei RAO Fang DENG Chun-yu 《园艺学报》2021,37(1):18-26
AIM To investigate the role of p300 in aging-related atrial fibrosis in human atrial fibroblasts （HAFs） and its potential mechanism. METHODS HAFs were obtained from human left atrial tissue, and the senescence model was established by cell passage. Senescence-associated β-galactosidase （SA-β-Gal） staining was used to detect the cell senescence, and Western blot was used to determine the protein levels of p300, p53, Smad3 and other senescence and fibrosis associated proteins in HAFs. RESULTS Compared to passage 3 HAFs, the proportion of senescent cells, and the protein levels of p300, p53, p-Smad3 and other senescence and fibrosis associated proteins were increased in HAFs at passage 7 and 11 （P <0.05）. After treated with curcumin （a p300 inhibitor） or transfection with p300 small-hairpin （sh） RNA plasmid, the protein levels of p300, and the senescence and fibrosis associated proteins were decreased in HAFs at passage 7（P <0.05）. Up-regulation of p300 by transfection with p300 over-expression plasmid increased the protein levels of p53, Smad3 and MMP-2 in HAFs at passage 3 （P <0.05）. CONCLUSION p300/p53/Smad3 signaling pathway plays an important role in aging-related atrial fibrosis in HAFs. 相似文献
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LUO Yuan-liang LI Meng-si TENG Jia-shuo DAI Xiao-meng TANG Xiang-xu XING Yun Lü Xiu-xiu 《园艺学报》2000,36(9):1543-1550
AIM To observe the effect of adriamycin/doxorubicin （DOX） on the production of inflammatory cytokines and collagen in cardiac fibroblasts and its mechanism. METHODS Neonatal SD rat cardiac fibroblasts were isolated, cultured, and identified by immunofluorescence staining with monoclonal antibodies against vimentin observed under a confocal laser-scanning microscope. The Cell Counting Kit-8 assay was used to detect the toxicity of DOX on cardiac fibroblasts, and flow cytometry with annexin V-FITC/PI double staining was used to detect apoptosis. ELISA was used to detect the release of inflammatory factors in the supernatant of cultured cells. Immunofluorescence labeling assay was used to detected α-smooth muscle actin （α-SMA） expression and mitochondrial reactive oxygen species （mROS） in the cells. Western blot was used to detect the expression of nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） inflammasome-related proteins in cardiac fibroblasts. RESULTS （1） Compared with the control group, DOX inhibited the proliferation of cardiac fibroblasts （P <0.05）, but had no significant effect on apoptosis （P >0.05）. （2） Treatment with DOX promotes the release of proinflammatory factors interleukin-1β （IL-1β） and IL-6 in cardiac fibroblasts （P <0.05）. （3） The expression of α-SMA, collagen type I and transforming growth factor-β in DOX treatment group increased significantly compared with control group （P <0.05）. （4） Compared with the control group, the levels of mROS, cellular NLRP3 and cleaved caspase-1 in cardiac fibroblasts increased significantly after DOX treatment. CONCLUSION Doxorubicin promotes cardiac fibroblasts to secrete IL-1β and collagen type I by promoting mROS production and activating NLRP3 inflammasome. 相似文献
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Leib MS Dinnel H Ward DL Reimer ME Towell TL Monroe WE 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2001,15(6):547-552
Endoscopic balloon dilation of benign esophageal strictures was performed in 18 dogs and 10 cats with a median age of 4 years. Stricture formation was associated with a recent anesthetic episode in 18 patients. Regurgitation was the most common clinical sign and was present a median of 4 weeks before dilation. Most animals had a single stricture; median diameter was 5 mm, and median length was 1 cm. Esophagitis and mucosal fibrosis were detected in 9 patients each. Dilation was performed with progressively increasing diameter balloons, from 6 to 20 mm. After dilation, mucosal hemorrhage was mild to moderate in most patients. Esophageal perforation was the only serious complication and occurred in 1 patient. Postdilation therapy consisted of administration of cimetidine, metoclopramide, sucralfate, and prednisone in most animals. The median number of dilation procedures performed in each animal was 2, with a range of 1-5. The median interval between dilations was 13 days. Stricture diameter markedly increased with subsequent dilations. Median duration of follow-up was 131 weeks. A successful outcome occurred in 88% of patients, with most animals able to eat canned, mashed, or dry food without regurgitation. Mucosal fibrosis was associated with a better clinical response score, while increasing age was weakly associated with fewer dilations. The dilation protocol used in this group of animals was safe and efficacious. 相似文献
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Serpin peptidase inhibitor clade E member 2 (SerpinE2), a member of serine peptidase inhibitor super family, regulates multiple serine proteases. Extracellular matrix (ECM) plays an important role in stem cell differentiation, signal transduction, tumor metastasis, osteoarthritis physiological and pathological processes and so on. SerpinE2 regulates the protein of extracellular matrix by serine protease system and matrix metalloproteinase (MMP) system. In this paper, we elaborate the effect of SerpinE2 on metabolism of extracellular matrix, and it will provide new ideas to find new therapeutic targets. 相似文献
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LIU Yan-li QIAO Liang ZHANG Jin-zhu YANG Fen YAN Yan YAN Xin LIN Jun-tang 《园艺学报》2016,32(8):1435-1439
AIM: To investigate the renal function and pathological changes in Npc1 mutant (Npc1-/-) mice. METHODS: Different genotypes of Niemann-Pick disease type C1 (Npc1) mice were identified by PCR. Subsequently, the renal function of Npc1-/- and Npc1+/+ mice at postnatal day 60 (P60) was evaluated by measuring the activity and content of important indicators in the serum including ALT, AST, LDH, urea, UA and Cr. Furthermore, β-galactosidase staining and Masson staining were performed to examine the aging and fibrosis of the renal tissues, respectively. RESULTS: Compared with the Npc1+/+ mice, the body weight and kidney weight had a significant reduction (P<0.01) in the Npc1-/- mice. The results of hepatic and renal functions showed that the activities of ALT, AST and LDH, and contents of urea, UA and Cr had marked increases (P<0.05) in the Npc1-/-mice. Moreover, the results of senescence-associated β-galactosidase staining in the renal tissues demonstrated accelerated aging in the Npc1-/- mice (P<0.01), and these results were confirmed by Masson staining, which clearly showed the formation of collagen fibers (P<0.01).CONCLUSION: Mutation of the Npc1 gene results in abnormal lipid metabolism, which accelerates kidney senescence by promoting fibrosis in the renal tissue and subsequently causes reduction in renal function. 相似文献
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Carrie M. Van De Wiele DVM Daniel F. Hogan DVM Henry W. Green III DVM Nolie K. Parnell DVM 《Journal of Veterinary Cardiology》2008,10(2):155-161
Superior vena caval syndrome is a rare, but reported complication of transvenous pacemaker implantation in humans. This syndrome can occur secondary to fibrotic and/or thrombotic obstruction of venous blood flow into the right atrium. The therapeutic approach depends on the suspicion of the presence of an active thrombus and may include antithrombotics, angioplasty and/or surgical venoplasty. We describe two dogs that developed severe pleural effusion secondary to stricture formation in the cranial vena cava 4 years after dual chamber transvenous pacemaker implantation. The stenosis was most likely due to fibrosis secondary to the transvenous pacemaker leads. Balloon angioplasty of the lesion resulted in resolution of the pleural effusion in both patients. Balloon angioplasty appears to be a viable therapeutic approach in dogs with cranial vena caval syndrome caused by focal stenotic lesions. 相似文献
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