Dentin matrix metalloproteinases (MMPs) are a family of host-derived proteolytic enzymes trapped within mineralized dentin matrix, which have the ability to hydrolyze the organic matrix of demineralized dentin. Afte...Dentin matrix metalloproteinases (MMPs) are a family of host-derived proteolytic enzymes trapped within mineralized dentin matrix, which have the ability to hydrolyze the organic matrix of demineralized dentin. After bonding with resins to dentin there are usually some exposed collagen fibrils at the bottom of the hybrid layer owing to imperfect resin impregnation of the demineralized dentin matrix. Exposed collagen fibrils might be affected by MMPs inducing hydrolytic degradation, which might result in reduced bond strength.Most MMPs are synthesized and released from odontoblasts in the form of proenzymes, requiring activation to degrade extracellular matrix components. Unfortunately, they can be activated by modem self-etch and etch-and-rinse adhe- sives. The aim of this review is to summarize the current knowledge of the role of dentinal host-derived MMPs in dentin matrix degradation. We also discuss various available MMP inhibitors, especially chlorhexidine, and suggest that they could provide a potential pathway for inhibiting collagen degradation in bonding interfaces thereby increasing dentin bonding durability.展开更多
基质金属蛋白酶(matrixmetalloproteinases,MMPs)和基质金属蛋白酶组织抑制剂(tissue in-hibitors of metalloproteinases,TIMPs)在医学的多个领域都得到了广泛的研究。随着近年来对MMPs与TIMPs在牙本质-牙髓复合体中研究的开展,发现它...基质金属蛋白酶(matrixmetalloproteinases,MMPs)和基质金属蛋白酶组织抑制剂(tissue in-hibitors of metalloproteinases,TIMPs)在医学的多个领域都得到了广泛的研究。随着近年来对MMPs与TIMPs在牙本质-牙髓复合体中研究的开展,发现它们与牙齿的多种生理、病理反应都有着密切的联系。本文仅就MMPs。展开更多
To investigate the effects of TGF-β1 on the two gelatinases (MMP-2 and MMP-9), and their roles in lung remodeling after irradiation-induced lung injury. Expressions of TGF-β1 were measured with western blot, and e...To investigate the effects of TGF-β1 on the two gelatinases (MMP-2 and MMP-9), and their roles in lung remodeling after irradiation-induced lung injury. Expressions of TGF-β1 were measured with western blot, and expressions of MMP-2 and MMP-9 were analyzed with zymography in a TGF-β1 transgenic mouse model after thoracic irradiation with 12 Gy. We found expressions of TGF-β1 in the lung from the transgenic mice were three folds as compared to those from control mice. With densitometrical analysis, we found a significant decrease in MMP-9 activity in lung homogenates from the transgenic mice as compared with those from non-transgenic control mice 8 weeks after sham-irradiation (relative MMP-9 activity: C: 1. 000±0. 1091; TG: 0. 4772±0. 470 (n=8, P〈0.05). But MMP-2 was constitutively expressed in the lung homogenates from the transgenic mice as compared to those from control mice 8 weeks after sham-irradiation (relative MMP-2 activity 8 weeks after sham-irradiation: C: 1. 000±0. 1556, TG: 1. 0075±0. 1472). Eight weeks after thoracic irradiation with 12 Gy, we observed a significant increase of MMP-2 and MMP-9 activity in lung homogenates from both transgenic and normal mice. In TGF-β1 transgenic mice relative MMP-9 activity was increased to 1. 5321±0. 2217 folds 8 weeks after thoracic irradiation with 12 Gy as compared to those after sham-irradiation (1. 000±0. 2153), and relative MMP-2 activity was increased to 1. 7142 ± 0. 4231 folds. Our results show that TGF-β1 itself down-regulates activity of MMP-9, thereby decreases ECM degradation in lungs of TGF-β1 transgenic mice. Also we find that ionizing irradiation upregulates both MMP-2 and MMP-9 activity. Over-expressions of MMP-9 and MMP-2 after lung irradiation are involved in the inflammatory response associated with radiation-induced lung injury, and maybe further in radiation-induced lung fibrosis.展开更多
Matrix metalloproteinases(MMPs) play an essential role in development and tissue remodeling of living organisms. However, the overexpression of MMPs has lead to a series of diseases, such as cancer, arthritis, and a...Matrix metalloproteinases(MMPs) play an essential role in development and tissue remodeling of living organisms. However, the overexpression of MMPs has lead to a series of diseases, such as cancer, arthritis, and atherosclerosis; and inhibition of MMPs may have therapeutic benefits. The discovery of MMP inhibitors from herbal has become a prospective event. We showed that the extract of Polygoni multiflori caulis from ethyl acetate or water(ethyl acetate extract and water extract) can inhibit the activities of MMPs 9, 14, and 16 in a dose-dependent manner and n-butyl alcohol extract of it can also inhibit these MMPs. Furthermore, we found that n-butyl alcohol extract and water extract of it influence the cell viability. These discoveries may contribute to the development of MMP in- hibitors for the therapy of a variety of pathological conditions.展开更多
Extracellular matrix(ECM)is characterized as widespread,abundant,and pluripotent.Among ECM members,collagen is widely accepted as one of the most prominent components for its essential structural property that can pro...Extracellular matrix(ECM)is characterized as widespread,abundant,and pluripotent.Among ECM members,collagen is widely accepted as one of the most prominent components for its essential structural property that can provide a scaffold for other components of ECM and the rich biological functions,which has been extensively used in tissue engineering.Emerging evidence has shown that the balance of ECM degradation and remodeling is vital to regulations of maternal-fetal interface including menstrual cycling,decidualization,embryo implantation and pregnancy maintenance.Moreover,disorders in these events may eventually lead to failure of pregnancy.Although the improvement of assisted conception and embryo culture technologies bring hope to many infertile couples,some unfavorable outcomes,such as recurrent implantation failure(RIF),recurrent pregnancy loss(RPL)or recurrent miscarriage(RM),keep troubling the clinicians and patients.Recently,in vitro three-dimensional(3D)model mimicking the microenvironment of the maternal-fetal interface is developed to investigate the physiological and pathological conditions of conception and pregnancy.The progress of this technology is based on clarifying the role of ECM in the endometrium and the interaction between endometrium and conceptus.Focusing on collagen,the present review summarized the degradation and regulation of ECM and its role in normal menstruation,endometrium receptivity and unsatisfying events occurring in infertility treatments,as well as the application in therapeutic approaches to improve pregnancy outcomes.More investigations about ECM focusing on the maternal-fetal interface interaction with mesenchymal stem cells or local immunoregulation may inspire new thoughts and advancements in the clinical application of infertility treatments.展开更多
Objective To study the effects of MMP-9 (Matrix Metalloproteinase-9, MMP-9) in the pathogenesis of abdominal aortic aneurysms (AAAs) by localizing the expression of MMP-9 in the aneurysmal tissues. Methods By means of...Objective To study the effects of MMP-9 (Matrix Metalloproteinase-9, MMP-9) in the pathogenesis of abdominal aortic aneurysms (AAAs) by localizing the expression of MMP-9 in the aneurysmal tissues. Methods By means of immunohistochemistry, the frozen sections(5 μ m) with aneurysmal tissues (n=10) were incubated with MMP-9 antibody-added agents, then the sections were stained and observed under the microscope to localize the expression of MMP-9, which displayed a brown precipitate within the arterial walls. The normal arterial wall tissues(n=10) and the diseased arterial wall tissues from the arterial occlusive diseases (AODs) (n=15) were also immunized exactly the same way as control. Results A quantity of positive granules which appeared within the aortic media showed the strong expression of MMP-9 in the AAAs, with the positive rate reaching 95%(19/20), while no expression of MMP-9 was observed in the normal artery. However, the scattered distributed positive granules were seen within the arterial wall of some cases of the AODs, implying the weak positive expression of MMP-9 in this disease with the positive rate of 26.7%(4/15). There was a significant difference of the expression of MMP-9 within the arterial wall between the AAAs and AODs(P<0.01). Conclusion High expression of MMP-9 within the aortic media faciliatates the degradation of collagen and elastin fibres and subsequent dilation of the aortic artery ,thus playing an important role in the pathogenesis of AAAs. To refrain MMP-9 from enhanced expressing within the aortic wall is of clinical significance in the prevention and treatment of AAAs.展开更多
Oxidative stress is linked to increased risk of gastric cancer and matrix metalloproteinases (MMPs) are important in the invasion and metastasis of gastric cancer. We aimed to analyze the effect of the accumulation ...Oxidative stress is linked to increased risk of gastric cancer and matrix metalloproteinases (MMPs) are important in the invasion and metastasis of gastric cancer. We aimed to analyze the effect of the accumulation of oxidative stress in the gastric cancer MKN-45 and 23132/87 cells following hydrogen peroxide (H202) exposure on the expression patterns of MMP-1, MMP-3, MMP-7, MMP-9, MMP-10, MMP- 1 1, MMP- 12, MMP-14, MMP- 15, MMP- 17, MMP-23, MMP-28, and β-catenin genes. Methods: The mRNA transcripts in the cells were determined by RT-PCR. Following H202 exposure, oxidative stress in the viable cells was analyzed by 2',7'-dichlorofluorescein diaeetate (DCFH-DA). Caffeie acid phenethyl ester (CAPE) was used to eliminate oxidative stress and the consequence of H2O2 exposure and its removal on the expressions of the genes were evaluated by quantitative real-time PCR. Results: The expressions of MMP-1, MMP-7, MMP-14, MMP-15, MMP-17 and β-catenin in MKN-45 cells and only the expression of MMP-15 in 23132/87 cells were increased. Removal of the oxidative stress resulted in decrease in the expressions of MMP genes of which the expressions were increased after H202 exposure. β-catenin, a transcription factor for many genes including MMPs, also displayed decreased levels of expression in both of the cell lines following CAPE treatment. Conclusions: Our data suggest that there is a remarkable link between the accumulation of oxidative stress and the increased expressions of MMP genes in the gastric cancer cells and MMPs should be considered as potential targets of therapy in gastric cancers due to its continuous exposure to oxidative stress.展开更多
文摘Dentin matrix metalloproteinases (MMPs) are a family of host-derived proteolytic enzymes trapped within mineralized dentin matrix, which have the ability to hydrolyze the organic matrix of demineralized dentin. After bonding with resins to dentin there are usually some exposed collagen fibrils at the bottom of the hybrid layer owing to imperfect resin impregnation of the demineralized dentin matrix. Exposed collagen fibrils might be affected by MMPs inducing hydrolytic degradation, which might result in reduced bond strength.Most MMPs are synthesized and released from odontoblasts in the form of proenzymes, requiring activation to degrade extracellular matrix components. Unfortunately, they can be activated by modem self-etch and etch-and-rinse adhe- sives. The aim of this review is to summarize the current knowledge of the role of dentinal host-derived MMPs in dentin matrix degradation. We also discuss various available MMP inhibitors, especially chlorhexidine, and suggest that they could provide a potential pathway for inhibiting collagen degradation in bonding interfaces thereby increasing dentin bonding durability.
文摘基质金属蛋白酶(matrixmetalloproteinases,MMPs)和基质金属蛋白酶组织抑制剂(tissue in-hibitors of metalloproteinases,TIMPs)在医学的多个领域都得到了广泛的研究。随着近年来对MMPs与TIMPs在牙本质-牙髓复合体中研究的开展,发现它们与牙齿的多种生理、病理反应都有着密切的联系。本文仅就MMPs。
文摘To investigate the effects of TGF-β1 on the two gelatinases (MMP-2 and MMP-9), and their roles in lung remodeling after irradiation-induced lung injury. Expressions of TGF-β1 were measured with western blot, and expressions of MMP-2 and MMP-9 were analyzed with zymography in a TGF-β1 transgenic mouse model after thoracic irradiation with 12 Gy. We found expressions of TGF-β1 in the lung from the transgenic mice were three folds as compared to those from control mice. With densitometrical analysis, we found a significant decrease in MMP-9 activity in lung homogenates from the transgenic mice as compared with those from non-transgenic control mice 8 weeks after sham-irradiation (relative MMP-9 activity: C: 1. 000±0. 1091; TG: 0. 4772±0. 470 (n=8, P〈0.05). But MMP-2 was constitutively expressed in the lung homogenates from the transgenic mice as compared to those from control mice 8 weeks after sham-irradiation (relative MMP-2 activity 8 weeks after sham-irradiation: C: 1. 000±0. 1556, TG: 1. 0075±0. 1472). Eight weeks after thoracic irradiation with 12 Gy, we observed a significant increase of MMP-2 and MMP-9 activity in lung homogenates from both transgenic and normal mice. In TGF-β1 transgenic mice relative MMP-9 activity was increased to 1. 5321±0. 2217 folds 8 weeks after thoracic irradiation with 12 Gy as compared to those after sham-irradiation (1. 000±0. 2153), and relative MMP-2 activity was increased to 1. 7142 ± 0. 4231 folds. Our results show that TGF-β1 itself down-regulates activity of MMP-9, thereby decreases ECM degradation in lungs of TGF-β1 transgenic mice. Also we find that ionizing irradiation upregulates both MMP-2 and MMP-9 activity. Over-expressions of MMP-9 and MMP-2 after lung irradiation are involved in the inflammatory response associated with radiation-induced lung injury, and maybe further in radiation-induced lung fibrosis.
基金Supported by the National Natural Science Foundation of China(No.30571656).
文摘Matrix metalloproteinases(MMPs) play an essential role in development and tissue remodeling of living organisms. However, the overexpression of MMPs has lead to a series of diseases, such as cancer, arthritis, and atherosclerosis; and inhibition of MMPs may have therapeutic benefits. The discovery of MMP inhibitors from herbal has become a prospective event. We showed that the extract of Polygoni multiflori caulis from ethyl acetate or water(ethyl acetate extract and water extract) can inhibit the activities of MMPs 9, 14, and 16 in a dose-dependent manner and n-butyl alcohol extract of it can also inhibit these MMPs. Furthermore, we found that n-butyl alcohol extract and water extract of it influence the cell viability. These discoveries may contribute to the development of MMP in- hibitors for the therapy of a variety of pathological conditions.
基金the Research project of Science&Technology Department of Sichuan Province(Y.Z.,Grant No.2021YJ0416)project of Chengdu Science and Technology Bureau,(Y.Z.,Grant No.2021-YF05-02110-SN)+4 种基金National Natural Science Foundation of China(Y.Z.,Grant No.82001496)China Postdoctoral Science Foundation(Y.Z.,Grant No.2020M680149,2020T130087ZX)China Postdoctoral Science Foundation(C.C.,Grant No.2021M702223)Shenzhen Science and Technology Innovation Committee(C.C.,Grant No.JCYJ20210324105808022)the Research Team of Female Reproductive Health and Fertility Preservation(W.Q.,Grant No.SZSM201612065).
文摘Extracellular matrix(ECM)is characterized as widespread,abundant,and pluripotent.Among ECM members,collagen is widely accepted as one of the most prominent components for its essential structural property that can provide a scaffold for other components of ECM and the rich biological functions,which has been extensively used in tissue engineering.Emerging evidence has shown that the balance of ECM degradation and remodeling is vital to regulations of maternal-fetal interface including menstrual cycling,decidualization,embryo implantation and pregnancy maintenance.Moreover,disorders in these events may eventually lead to failure of pregnancy.Although the improvement of assisted conception and embryo culture technologies bring hope to many infertile couples,some unfavorable outcomes,such as recurrent implantation failure(RIF),recurrent pregnancy loss(RPL)or recurrent miscarriage(RM),keep troubling the clinicians and patients.Recently,in vitro three-dimensional(3D)model mimicking the microenvironment of the maternal-fetal interface is developed to investigate the physiological and pathological conditions of conception and pregnancy.The progress of this technology is based on clarifying the role of ECM in the endometrium and the interaction between endometrium and conceptus.Focusing on collagen,the present review summarized the degradation and regulation of ECM and its role in normal menstruation,endometrium receptivity and unsatisfying events occurring in infertility treatments,as well as the application in therapeutic approaches to improve pregnancy outcomes.More investigations about ECM focusing on the maternal-fetal interface interaction with mesenchymal stem cells or local immunoregulation may inspire new thoughts and advancements in the clinical application of infertility treatments.
文摘Objective To study the effects of MMP-9 (Matrix Metalloproteinase-9, MMP-9) in the pathogenesis of abdominal aortic aneurysms (AAAs) by localizing the expression of MMP-9 in the aneurysmal tissues. Methods By means of immunohistochemistry, the frozen sections(5 μ m) with aneurysmal tissues (n=10) were incubated with MMP-9 antibody-added agents, then the sections were stained and observed under the microscope to localize the expression of MMP-9, which displayed a brown precipitate within the arterial walls. The normal arterial wall tissues(n=10) and the diseased arterial wall tissues from the arterial occlusive diseases (AODs) (n=15) were also immunized exactly the same way as control. Results A quantity of positive granules which appeared within the aortic media showed the strong expression of MMP-9 in the AAAs, with the positive rate reaching 95%(19/20), while no expression of MMP-9 was observed in the normal artery. However, the scattered distributed positive granules were seen within the arterial wall of some cases of the AODs, implying the weak positive expression of MMP-9 in this disease with the positive rate of 26.7%(4/15). There was a significant difference of the expression of MMP-9 within the arterial wall between the AAAs and AODs(P<0.01). Conclusion High expression of MMP-9 within the aortic media faciliatates the degradation of collagen and elastin fibres and subsequent dilation of the aortic artery ,thus playing an important role in the pathogenesis of AAAs. To refrain MMP-9 from enhanced expressing within the aortic wall is of clinical significance in the prevention and treatment of AAAs.
基金granted by the Scientific and Technical Research Council of Turkey (TUBITAK) under the project number 105S352 (SBAG-K-110)by the Scientific Research Fund of Fatih University under the project number P50030703
文摘Oxidative stress is linked to increased risk of gastric cancer and matrix metalloproteinases (MMPs) are important in the invasion and metastasis of gastric cancer. We aimed to analyze the effect of the accumulation of oxidative stress in the gastric cancer MKN-45 and 23132/87 cells following hydrogen peroxide (H202) exposure on the expression patterns of MMP-1, MMP-3, MMP-7, MMP-9, MMP-10, MMP- 1 1, MMP- 12, MMP-14, MMP- 15, MMP- 17, MMP-23, MMP-28, and β-catenin genes. Methods: The mRNA transcripts in the cells were determined by RT-PCR. Following H202 exposure, oxidative stress in the viable cells was analyzed by 2',7'-dichlorofluorescein diaeetate (DCFH-DA). Caffeie acid phenethyl ester (CAPE) was used to eliminate oxidative stress and the consequence of H2O2 exposure and its removal on the expressions of the genes were evaluated by quantitative real-time PCR. Results: The expressions of MMP-1, MMP-7, MMP-14, MMP-15, MMP-17 and β-catenin in MKN-45 cells and only the expression of MMP-15 in 23132/87 cells were increased. Removal of the oxidative stress resulted in decrease in the expressions of MMP genes of which the expressions were increased after H202 exposure. β-catenin, a transcription factor for many genes including MMPs, also displayed decreased levels of expression in both of the cell lines following CAPE treatment. Conclusions: Our data suggest that there is a remarkable link between the accumulation of oxidative stress and the increased expressions of MMP genes in the gastric cancer cells and MMPs should be considered as potential targets of therapy in gastric cancers due to its continuous exposure to oxidative stress.