Objective: To study the effects of quercetin (QU) on matrix metallo-proteinases (MMPs) , the tissue inhibitor of matalloproteinase-1 (TIMP-1) , procollagen I and 2 proteoglycans (decorin and biglycan) mRNA expression ...Objective: To study the effects of quercetin (QU) on matrix metallo-proteinases (MMPs) , the tissue inhibitor of matalloproteinase-1 (TIMP-1) , procollagen I and 2 proteoglycans (decorin and biglycan) mRNA expression in cultured rat hepatic stellate cell line HSC-T6 cells. Methods: Cells were treated with different concentrations of QU (12. 5, 25, 50 μmol/L) or drug solvent (0. 1 % Me2SO) for 24 h. mRNA expression was determined by reverse transcription polymerase chain reaction (RT-PCR). Results: QU (12.5 - 50 μmol/L) enhanced collagenase (rat MMP-13) and membrane typel-MMP (MMP-14) mRNA expression, decreased procollagen I mRNA expression in a concentration-dependent manner, but did not affect gelatinase-A (MMP-2) , TIMP-1, decorin and biglycan expression. Conclusion: QU may decrease matrix deposition and increase matrix degradation, which might be beneficial to liver fibrosis.展开更多
OBJECTIVES: To detect the level of matrix metalloproteinase-2 (MMP-2) mRNA and the tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA in bladder transitional cell carcinoma (BTCC), and to estimate the prognosis for...OBJECTIVES: To detect the level of matrix metalloproteinase-2 (MMP-2) mRNA and the tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA in bladder transitional cell carcinoma (BTCC), and to estimate the prognosis for bladder tumor based on the quality and quantity of MMP-2 and TIMP-2 mRNA. METHODS: Thirty-five samples of human BTCC and 15 normal fresh bladder tissues were studied by RT-PCR analysis followed by computer-assisted image analysis. RESULTS: The level of the MMP-2 mRNA in BTCC was significantly increased compared with that in normal bladder epithelium. The positive rates of MMP-2 and TIMP-2 mRNA were 71.4% and 65.7% in BTCC, and 66.7% and 60.0% in the normal bladder wall. The expression intensity of the MMP-2 mRNA by image analysis tended to increase with tumor grading and staging, which showed statistical significance. Similarly, the MMP-2 to TIMP-2 ratio also showed statistically significant difference between normal bladder tissue and bladder carcinoma (P展开更多
Aortic dissection （AD） is a devastating, heterogeneous condition of aorta. The homeostasis between collagens and matrix metalloproteases （MMPs）/tissue inhibitors of MMPs （TIMPs） system in the extracellular matri...Aortic dissection （AD） is a devastating, heterogeneous condition of aorta. The homeostasis between collagens and matrix metalloproteases （MMPs）/tissue inhibitors of MMPs （TIMPs） system in the extracellular matrix plays an important role for structure and functions of aorta. However, our knowledge on association between variants of genes in this system and pathogenesis of AD is very limited. We analyzed all yet known coding human genes of collagens （45 genes）, MMPs/TIMPs （27 genes） in 702 sporadic AD patients and in 163 matched healthy controls, by using massively targeted next-generation and Sanger sequencing. To define the pathogenesis of potential disease-causing candidate genes, we performed transcriptome sequencing and pedigree co-segregation analysis in some genes and generated Col5a2 knockout rats. We identified 257 pathogenic or likely pathogenic variants which involved 88.89% （64/72） genes in collagens-MMPs/TIMPs system and accounted for 31.05% （218/702） sporadic AD patients. In them, 84.86% patients （185/218） carried one variant, 12.84% two variants and 2.30% more than two variants. Importantly, we identified 52 novel probablY pathogenic loss-of-function （LOF） variants （20 nonsense, 16 frameshift, 14 splice sites, one stop-loss, one initiation codon） in 11.06% （50/452） AD patients, which were absent in 163 controls （P=2.5-10-5）. Transcriptome sequencing revealed that identified variants induced dyshomeostasis in expression of collagens-TIMPs/MMPs systems. The Col5a2-/- rats manifested growth retardation and aortic dysplasia. Our study provides a first comprehensive map of genetic alterations in collagens-MMPs/TIMPs system in sporadic AD patients and suggests that variants of these genes contribute largely to AD pathogenesis.展开更多
OBJECTIVE:To investigate the effect of Chinese medicines using the warming Yang and removing blood stasis method on levels of matrix metalloproteinases(MMPs)/tissue inhibitor metalloproteinases(TIMPs) secreted by cult...OBJECTIVE:To investigate the effect of Chinese medicines using the warming Yang and removing blood stasis method on levels of matrix metalloproteinases(MMPs)/tissue inhibitor metalloproteinases(TIMPs) secreted by cultured endometrial cells from patients with endometriosis.METHODS:Ectopic and eutopic endometrial cells obtaind from 15 endometriosis patients were cultured in vitro,and divided randomly into five groups:high dose;moderate dose;low dose;nemestran;blank control.The three dose groups were treated with a decoction prepared according to the principle of warming Yang and removing blood stasis;nemestran and 0.9%NaCI were administered to the nemestran group and balnk control group,respectively.Eutopic endometrial cells obtaind from 10 hysteromyoma patients were cultured in vitro,as the normal control group,0.9%NaCI were administered to the normal control group.Cell culture supernatants were collected and levels of matrix metalloproteinase-1(MMP-1),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),tissue inhibitor metalloproteinase-1(TIMP-1) and tissue inhibitor metalloproteinase-2(TIMP-2) detected by enzyme-linked immuno sorbent assay(ELISA).RESULTS:Compared with the normal control group,levels of MMP-1,MMP-2,and MMP-9 in eutopic and ectopic endometrium cell supernatants in the blank control group were increased,whereas levels of TIMP-1 and TIMP-2 were decreased(P <0.05).Compared with the blank control group,levels of MMP-1 and MMP-2 in ectopic and eutopic endometrium cell supernatants cultured in low-dose,middle-dose,and high-dose groups were decreased,whereas levels of TIMP-1 and TIMP-2 were increased significantly(P < 0.05).CONCLUSION:The warming Yang and removing blood stasis method affects expression of MMPs andTIMPs.展开更多
文摘Objective: To study the effects of quercetin (QU) on matrix metallo-proteinases (MMPs) , the tissue inhibitor of matalloproteinase-1 (TIMP-1) , procollagen I and 2 proteoglycans (decorin and biglycan) mRNA expression in cultured rat hepatic stellate cell line HSC-T6 cells. Methods: Cells were treated with different concentrations of QU (12. 5, 25, 50 μmol/L) or drug solvent (0. 1 % Me2SO) for 24 h. mRNA expression was determined by reverse transcription polymerase chain reaction (RT-PCR). Results: QU (12.5 - 50 μmol/L) enhanced collagenase (rat MMP-13) and membrane typel-MMP (MMP-14) mRNA expression, decreased procollagen I mRNA expression in a concentration-dependent manner, but did not affect gelatinase-A (MMP-2) , TIMP-1, decorin and biglycan expression. Conclusion: QU may decrease matrix deposition and increase matrix degradation, which might be beneficial to liver fibrosis.
文摘OBJECTIVES: To detect the level of matrix metalloproteinase-2 (MMP-2) mRNA and the tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA in bladder transitional cell carcinoma (BTCC), and to estimate the prognosis for bladder tumor based on the quality and quantity of MMP-2 and TIMP-2 mRNA. METHODS: Thirty-five samples of human BTCC and 15 normal fresh bladder tissues were studied by RT-PCR analysis followed by computer-assisted image analysis. RESULTS: The level of the MMP-2 mRNA in BTCC was significantly increased compared with that in normal bladder epithelium. The positive rates of MMP-2 and TIMP-2 mRNA were 71.4% and 65.7% in BTCC, and 66.7% and 60.0% in the normal bladder wall. The expression intensity of the MMP-2 mRNA by image analysis tended to increase with tumor grading and staging, which showed statistical significance. Similarly, the MMP-2 to TIMP-2 ratio also showed statistically significant difference between normal bladder tissue and bladder carcinoma (P
基金supported by the National Natural Science Foundation of China(91439203)National Key Basic Research Program of China(2012CB518004,2012CB517801)
文摘Aortic dissection （AD） is a devastating, heterogeneous condition of aorta. The homeostasis between collagens and matrix metalloproteases （MMPs）/tissue inhibitors of MMPs （TIMPs） system in the extracellular matrix plays an important role for structure and functions of aorta. However, our knowledge on association between variants of genes in this system and pathogenesis of AD is very limited. We analyzed all yet known coding human genes of collagens （45 genes）, MMPs/TIMPs （27 genes） in 702 sporadic AD patients and in 163 matched healthy controls, by using massively targeted next-generation and Sanger sequencing. To define the pathogenesis of potential disease-causing candidate genes, we performed transcriptome sequencing and pedigree co-segregation analysis in some genes and generated Col5a2 knockout rats. We identified 257 pathogenic or likely pathogenic variants which involved 88.89% （64/72） genes in collagens-MMPs/TIMPs system and accounted for 31.05% （218/702） sporadic AD patients. In them, 84.86% patients （185/218） carried one variant, 12.84% two variants and 2.30% more than two variants. Importantly, we identified 52 novel probablY pathogenic loss-of-function （LOF） variants （20 nonsense, 16 frameshift, 14 splice sites, one stop-loss, one initiation codon） in 11.06% （50/452） AD patients, which were absent in 163 controls （P=2.5-10-5）. Transcriptome sequencing revealed that identified variants induced dyshomeostasis in expression of collagens-TIMPs/MMPs systems. The Col5a2-/- rats manifested growth retardation and aortic dysplasia. Our study provides a first comprehensive map of genetic alterations in collagens-MMPs/TIMPs system in sporadic AD patients and suggests that variants of these genes contribute largely to AD pathogenesis.
基金Supported by the Innovation Fundation of Chinese Medicine research,Guangzhou University of Chinese Medicine!Effect of Chinese Medicines in the Warming Yang and Removing Blood Stasis Method on the Biological Characteristics of Cultured Endometrial Cells from Patients with Endometriosis,No.K0080053)the Natural Science Foundation of Heibei Province of China(Effect of Dang Gui Si Ni Jia Wu Zhu Yu Sheng Jiang Huang Jiu Decoction via NF-KBp65signaling pathway on the regulating endometrial Biological Characteristics of endometriosis.No.2015CFB590)
文摘OBJECTIVE:To investigate the effect of Chinese medicines using the warming Yang and removing blood stasis method on levels of matrix metalloproteinases(MMPs)/tissue inhibitor metalloproteinases(TIMPs) secreted by cultured endometrial cells from patients with endometriosis.METHODS:Ectopic and eutopic endometrial cells obtaind from 15 endometriosis patients were cultured in vitro,and divided randomly into five groups:high dose;moderate dose;low dose;nemestran;blank control.The three dose groups were treated with a decoction prepared according to the principle of warming Yang and removing blood stasis;nemestran and 0.9%NaCI were administered to the nemestran group and balnk control group,respectively.Eutopic endometrial cells obtaind from 10 hysteromyoma patients were cultured in vitro,as the normal control group,0.9%NaCI were administered to the normal control group.Cell culture supernatants were collected and levels of matrix metalloproteinase-1(MMP-1),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),tissue inhibitor metalloproteinase-1(TIMP-1) and tissue inhibitor metalloproteinase-2(TIMP-2) detected by enzyme-linked immuno sorbent assay(ELISA).RESULTS:Compared with the normal control group,levels of MMP-1,MMP-2,and MMP-9 in eutopic and ectopic endometrium cell supernatants in the blank control group were increased,whereas levels of TIMP-1 and TIMP-2 were decreased(P <0.05).Compared with the blank control group,levels of MMP-1 and MMP-2 in ectopic and eutopic endometrium cell supernatants cultured in low-dose,middle-dose,and high-dose groups were decreased,whereas levels of TIMP-1 and TIMP-2 were increased significantly(P < 0.05).CONCLUSION:The warming Yang and removing blood stasis method affects expression of MMPs andTIMPs.
