To investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-κB inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9).
Periodontitis is a group of inflammatory diseases affecting the tissues supporting the teeth that will progressively cause the loss of alveolar bone and periodontal ligaments and eventually the dentition. Activation of osteoclast activity by RANKL and released enzymes such as matrix metalloproteinases (MMPs) are among the factors involved in the destruction of the periodontium. However, the mechanisms regulating their production in periodontitis are poorly understood. Endothelin signaling via the activation of the endothelin-A receptor (EDNRA) by endothelin-1 may play a role in the disease since the expression of the receptor and ligand is elevated in the periodontal tissues of patients with periodontitis.
Matrix metalloproteinases (MMPs) are involved in the extracellular matrix (ECM) remodeling during human placentation and parturition and have been shown to be associated with oxidative stress. Placental regional changes in oxygen availability and oxidative stress indices may influence regional differences in expression of MMPs. This study examines the protein and mRNA levels of MMP-2 and MMP-9 in different regions of the placenta in normotensive control (NC) women and women with preeclampsia (PE). Fifty-two NC women and 43 women with PE (18 delivered at term [T-PE] and 25 delivered preterm [PT-PE]) were recruited. Placental samples were taken from four regions: central basal (CM), central chorionic (CF), peripheral basal (PM), and peripheral chorionic (PF). MMP protein and mRNA levels were measured by ELISA and quantitative real time PCR, respectively. MMP-2 protein levels were higher in all the placental regions (P < 0.05) from PT-PE group as compared to the respective regions from the NC and T-PE groups. MMP-9 mRNA levels were higher in CM region as compared to CF and PM regions (P < 0.05) in the NC group and compared to CF and PF regions (P < 0.05) in the T-PE group. The MMP-9 mRNA levels were lower in the CF region in the PT-PE and T-PE groups (P < 0.05) as compared to the NC group. Elevated levels of MMP-2 protein levels were observed in all regions of PT-PE placenta possibly influencing the degradation of placental ECM. Lower mRNA expression of MMP-9 both in PT-PE and T-PE may contribute to a disturbed placental vascularization.
Age-related macular degeneration (AMD) is a disease of the macula that significantly affects eyesight and leads to irreversible central vision loss. Recent studies have demonstrated that angiogenesis is the most important mechanism of AMD development. It is associated with extracellular remodeling involving different proteolytic systems, among them matrix metalloproteinases (MMPs), which play an essential role in the etiopathogenesis of AMD. The main objective of the present study was to determine the relationship between exudative AMD and MMP-2 (-1306 C/T) rs243865 polymorphism.
Liu and colleagues investigated the expression of matrix matalloproteinases (MMPs) in human periodontal ligament fibroblasts (hPDLFs) regulated by interleukin-12 (IL-12), a cytokine implicated in inflammatory and immune responses. They showed that IL-12 activates canonical NF-kappaB signalling leading to increased expression of MMP-1 (Interstitial collagenase), MMP-3 (stromelysin 1) and MMP-13 (collagenase 3), and to a smaller reduction in the expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) at both mRNA and protein levels, with corresponding changes in the secreted levels of these extracellular matrix-remodelling and immune regulatory metalloproteinases. Here, we comment on the possible mechanisms of IL-12-mediated transcriptional regulation of MMPs.
Transforming growth factor-beta (TGF-β) is critical for cell proliferation and differentiation in dental pulp. Here, we show the dynamic mechanisms of TGF-β in porcine dental pulp, odontoblasts and dentin. The mRNA of latent TGF-β1 and TGF-β3 is predominantly expressed in odontoblasts, whereas the mRNA expression level of latent TGF-β2 is high in dental pulp. TGF-β1 is a major isoform of TGF-β, and latent TGF-β1, synthesized in dental pulp, is primarily activated by matrix metalloproteinase 11 (MMP11). Activated TGF-β1 enhances the mRNA expression levels of MMP20 and full-length dentin sialophosphoprotein (DSPP) in dental pulp cells, coinciding with the induction of odontoblast differentiation. Latent TGF-β1 synthesized in odontoblasts is primarily activated by MMP2 and MMP20 in both odontoblasts and dentin. The activity level of TGF-β1 was reduced in the dentin of MMP20 null mice, although the amount of latent TGF-β1 expression did not change between wild-type and MMP20 null mice. TGF-β1 activity was reduced with the degradation of DSPP-derived proteins that occurs with ageing. We propose that to exert its multiple biological functions, TGF-β1 is involved in a complicated dynamic interaction with matrix metalloproteinases (MMPs) and/or DSPP-derived proteins present in dental pulp, odontoblasts and dentin.
Inhibitory Effects of Plumbagin on Retinal Pigment Epithelial Cell Epithelial-Mesenchymal Transition In Vitro and In Vivo
- Medical science monitor : international medical journal of experimental and clinical research
- Published over 2 years ago
BACKGROUND This study aimed to explore the effects of plumbagin (PLB) on epithelial-to-mesenchymal transition in retinal pigment epithelial (RPE) cells and in proliferative vitreoretinopathy (PVR) rabbit models. MATERIAL AND METHODS Rabbit RPE cells were exposed to various concentrations (0, 5, 15, and 25 µM) of PLB. Motility, migration, and invasion of PLB-treated cells were determined in vitro using Transwell chamber assays and scratch wound assays. The contractile ability was evaluated by cell contraction assay. Expression of matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT) markers were assessed by western blotting. Furthermore, PLB was injected in rabbit eyes along with RPE cells after gas compression of the vitreous. The presence of PVR was determined by indirect ophthalmoscopy on days 1, 7, 14, and 21 after injection. Also, optical coherence tomography (OCT), ultrasound images, electroretinograms (ERG), and histopathology were used to assess efficacy and toxicity. RESULTS PLB significantly inhibited the migration and invasion of RPE cells. The agent also markedly reduced cell contractive ability. Furthermore, PLB treatment resulted in the decreased expression of MMP-1, MMP2, α-SMA, and the protection of ZO-1. In addition, the PLB-treated eyes showed lower PVR grades than the untreated eyes in rabbit models. PLB exhibited a wide safety margin, indicating no evidence of causing retinal toxicity. CONCLUSIONS PLB effectively inhibited the EMT of rabbit RPE cells in vitro and in the experimental PVR models. The results open new avenues for the use of PLB in prevention and treatment of PVR.
The present study investigated the effects of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in transplantation-associated arteriosclerosis by observing their expression in transplanted aortas in rats. Allogenic and isogenic abdominal aortic transplantations were performed and grafts were removed from the recipients at the designated time points (day 7, 14, 28 and 56 post transplantation). Hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and western blot analysis were used to evaluate the grafts. Significant proliferation of the intima was observed in the allogenic transplantation groups (P<0.05). The expressions of MMPs and TIMPs in the allografts were significantly increased compared with the isografts, and the suppression of MMP2 in allografts reduced injury after transplantation. The present study concluded that the imbalance of MMPs and TIMPs led to the disturbance of synthesis and the degradation of the extracellular matrix and it may represent a key cause of chronic rejection.
The study was undertaken to examine mRNA expression and localization of selected matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), and the activity of MMPs in chicken postovulatory follicles (POFs) during their apoptotic regression. Apoptotic cells and apoptosis-related caspase expression and activity were examined as well. Chickens were sacrificed 2 h and 21 h after ovulation, and five POFs (POF1 to POF5) were isolated from the ovaries. It was found that the number of apoptotic cells (TUNEL-positive) increased along with follicle regression. The relative expression (RQ) of caspase-2, -3, -8 and -9 mRNA increased (P<0.05) in POF5, while the activity of all examined caspases elevated gradually (approximately 80-150%) reaching the highest level in POF3, and then slowly decreased to the value noted in POF1 (P<0.05 - P<0.001). Real-time polymerase chain reaction revealed different expression of MMP-2, -7, -9 and TIMP-2 and -3 on mRNA levels, and activity assay showed the changes in activity of MMP-2 and -9 in the POFs. Regression of the follicles was accompanied predominantly by an increase in the relative expression of MMP-2, and a decrease in TIMP-2 and -3 mRNAs (P<0.05 - P<0.001). The activity levels of MMP-2 and -9 showed pronounced changes during the examined period. During follicle regression elevated activity of MMP-2 and -9 was found (P<0.05 - P<0.001). Immunohistochemistry demonstrated tissue- and follicle-dependent immunoreactivity of the examined members of the MMP system. In summary, the results showing the apoptotic regression-related changes as well as tissue-dependent differences in the expression of selected MMPs and TIMPs, and activity of MMP-2 and MMP-9, point to the significance that these molecules might participate in the complex orchestration of chicken POF regression.
Matrix metalloproteinases (MMPs) such as gelatinases are differentially expressed in human tissues. These enzymes cleave specific substrates involved in cell signaling, tissue development and remodeling and tissue breakdown. Recent evidences show that gelatinases are crucial for normal dentin development and their activity is maintained throughout the entire tooth function in the oral cavity. Due to the lack of information about the exact location and activity of gelatinases in mature human dentin, the present study was designed to examine gelatinolytic levels in sound dentin. In situ zymography using confocal microscopy was performed on both mineralized and demineralized dentin samples. Sites presenting gelatinase activity were identified throughout the entire biological tissue pursuing different gelatinolytic levels for distinct areas: predentin and dentinal tubule regions presented higher gelatinolytic activity compared to intertubular dentin. Dentin regions with higher gelatinolytic activity immunohistochemically were partially correlated with MMP-2 expression. The maintenance of gelatinolytic activity in mature dentin may have biological implications related to biomineralization of predentin and tubular/peritubular dentinal regions, as well as regulation of defensive mechanisms of the dentin-pulp complex.