• Title/Summary/Keyword: Matrix metalloproteinase 2

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Alterations of mRNA and lncRNA profiles associated with the extracellular matrix and spermatogenesis in goats

  • Chen, Haolin;Miao Xiaomeng;Xu, Jinge;Pu, Ling;Li, Liang;Han, Yong;Mao, Fengxian;Ma, Youji
    • Animal Bioscience
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    • v.35 no.4
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    • pp.544-555
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    • 2022
  • Objective: Spermatozoa are produced within the seminiferous tubules after sexual maturity. The expression levels of mRNAs and lncRNAs in testicular tissues are different at each stage of testicular development and are closely related to formation of the extracellular matrix (ECM) and spermatogenesis. Therefore, we set out to study the expression of lncRNAs and mRNAs during the different developmental stages of the goat testis. Methods: We constructed 12 RNA libraries using testicular tissues from goats aged 3, 6, and 12 months, and studied the functions of mRNAs and lncRNAs using the gene ontogeny (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases. Relationships between differentially expressed genes (DEGs) were analyzed by lncRNA-mRNA co-expression network and protein-protein interaction network (PPI). Finally, the protein expression levels of matrix metalloproteinase 2 (MMP2), insulin-like growth factor 2 (IGF2), and insulin-like growth factor-binding protein 6 (IGFBP6) were detected by western blotting. Results: We found 23, 8, and 135 differentially expressed lncRNAs and 161, 12, and 665 differentially expressed mRNAs that were identified between 3 vs 6, 6 vs 12, and 3 vs 12 months, respectively. GO, KEGG, and PPI analyses showed that the differential genes were mainly related to the ECM. Moreover, MMP2 was a hub gene and co-expressed with the lncRNA TCONS-0002139 and TCONS-00093342. The results of quantitative reverse-transcription polymerase chain reaction verification were consistent with those of RNA-seq sequencing. The expression trends of MMP2, IGF2, and IGFBP6 protein were the same as that of mRNA, which all decreased with age. IGF2 and MMP2 were significantly different in the 3 vs 6-month-old group (p<0.05). Conclusion: These results improve our understanding of the molecular mechanisms involved in sexual maturation of the goat testis.

Inhibition of the Expression of Matrix Metalloproteinases in Articular Chondrocytes by Resveratrol through Affecting Nuclear Factor-Kappa B Signaling Pathway

  • Kang, Dong-Geun;Lee, Hyun Jae;Lee, Choong Jae;Park, Jin Sung
    • Biomolecules & Therapeutics
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    • v.26 no.6
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    • pp.560-567
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    • 2018
  • In the present study, we tried to examine whether resveratrol regulates the expression of matrix metalloproteinases (MMPs) through affecting nuclear factor-kappa B ($NF-{\kappa}B$) in articular chondrocytes. Rabbit articular chondrocytes were cultured in a monolayer, and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure interleukin-${\beta}$ ($IL-1{\beta}$)-induced gene expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), ADAMTS-5 and type II collagen. Effect of resveratrol on $IL-1{\beta}$-induced secretion of MMP-3 was investigated in rabbit articular chondrocytes using western blot analysis. To elucidate the action mechanism of resveratrol, effect of resveratrol on $IL-1{\beta}$-induced $NF-{\kappa}B$ signaling pathway was investigated in SW1353, a human chondrosarcoma cell line, by western blot analysis. The results were as follows: (1) resveratrol inhibited the gene expression of MMP-3, MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5, but increased the gene expression of type II collagen; (2) resveratrol reduced the secretion of MMP-3; (3) resveratrol inhibited $IL-1{\beta}$induced activation (phosphorylation) of inhibitory kappa B kinase (IKK), and thus phosphorylation and degradation of inhibitory kappa $B{\alpha}$ ($I{\kappa}B{\alpha}$); (4) resveratrol inhibited $IL-1{\beta}$-induced phosphorylation and nuclear translocation of $NF-{\kappa}B$ p65. This, in turn, led to the down-regulation of gene expression of MMPs in SW1353 cells. These results suggest that resveratrol can regulate the expression of MMPs through affecting $NF-{\kappa}B$ by directly acting on articular chondrocytes.

Expression of Matrix Metalloproteinase-10 at Invasive Front of Squamous Cell Carcinoma and Verrucous Carcinoma in the Oral Cavity

  • Kadeh, Hamideh;Saravani, Shirin;Heydari, Fatemeh;Keikha, Mohammad;Rigi, Vahab
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6609-6613
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    • 2015
  • Background: Matrix metalloproteinases (MMPs) are a family of zinc metalloproteinases capable of degrading components of connective tissues. MMP-10 is frequently expressed in human cancers. The aim of this study was to immunohistochemically evaluate its expression in oral squamous cell carcinoma (OSCC) and verrucous carcinoma (OVC). Materials and Methods: A retrospective analysis of 73 samples (31 OSCC, 22 OVC and 20 non-neoplastic epithelium) was performed. All samples were immunohistochemically stained with monoclonal MMP-10 antibody and expression levels and staining intensity were evaluated with respect to microscopic features. Data were analyzed by SPSS (V.21), Mann-Whitney and Kruskal Wallis tests. Results: MMP-10 was detected in all OSCC and OVC cases. The expression of MMP-10 in OSCC was intensive (score 3) and in OVC was low and moderate (score 1 and score 2) more frequently. Non- neoplastic epithelium did not show MMP-10 expression. Differences between groups was statistically significant (p<0.05). However, the expression of MMP-10 was not obviously different between various grades of OSCC. Conclusions: According to our study, MMP-10 protein can be important possible factor in the transformation of normal oral epithelium to OVC and OSCC, also the level of MMP-10 expression at invasion front of the lesions can be helpful in the differentiation of OVC and OSCC.

Low-Molecular-Weight Collagen Peptide Ameliorates Osteoarthritis Progression through Promoting Extracellular Matrix Synthesis by Chondrocytes in a Rabbit Anterior Cruciate Ligament Transection Model

  • Lee, Mun-Hoe;Kim, Hyeong-Min;Chung, Hee-Chul;Kim, Do-Un;Lee, Jin-Hee
    • Journal of Microbiology and Biotechnology
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    • v.31 no.10
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    • pp.1401-1408
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    • 2021
  • This study examined whether the oral administration of low-molecular-weight collagen peptide (LMCP) containing 3% Gly-Pro-Hyp with >15% tripeptide (Gly-X-Y) content could ameliorate osteoarthritis (OA) progression using a rabbit anterior cruciate ligament transection (ACLT) model of induced OA and chondrocytes isolated from a patient with OA. Oral LMCP administration (100 or 200 mg/kg/day) for 12 weeks ameliorated cartilage damage and reduced the loss of proteoglycan compared to the findings in the ACLT control group, resulting in dose-dependent (p < 0.05) improvements of the OARSI score in hematoxylin & eosin (H&E) and Safranin O staining. In micro-computed tomography analysis, LMCP also significantly (p < 0.05) suppressed the deterioration of the microstructure in tibial subchondral bone during OA progression. The elevation of IL-1β and IL-6 concentrations in synovial fluid following OA induction was dose-dependently (p < 0.05) reduced by LMCP treatment. Furthermore, immunohistochemistry illustrated that LMCP significantly (p < 0.05) upregulated type II collagen and downregulated matrix metalloproteinase-13 in cartilage tissue. Consistent with the in vivo results, LMCP significantly (p < 0.05) increased the mRNA expression of COL2A1 and ACAN in chondrocytes isolated from a patient with OA regardless of the conditions for IL-1β induction. These findings suggest that LMCP has potential as a therapeutic treatment for OA that stimulates cartilage regeneration.

Effects of Bombycis Corpus on Male Osteoporosis (백강잠(白殭蠶)이 남성 골다공증에 미치는 영향)

  • Kim, Ho Hyun;Ahn, Sang Hyun;Park, Sun Young
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.33 no.1
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    • pp.56-62
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    • 2019
  • To investigate the effect of Bombycis Corpus on male osteoporosis, we performed Dual Energy X-Ray Absorptiometry(DEXA) and histochemical methods. The animals were used ICR-based male mice of 8 weeks and 50 weeks, respectively. ICR male mice at 8 weeks were used in the control group, and ICR male mice at 50 weeks were used in aging group and Bombycis Corpus group(BC group). In the aging group, 0.5 ml of distilled water was administered once a day for 6 months. In BC group, Bombycis Corpus(0.78g/kg) was dissolved in distilled water for 6 months once a day. As a result, Bombycis Corpus decreased bone loss, increased bone density by reducing the loss of bone matrix in the femur due to aging, and increased osteoblast - induced osteopontin(OPN) and osteocalcin(OPC) positivite reaction. In addition, administration of Bombycis Corpus decreased Reaction of activation of nuclear factor kappa B ligand(RANKL) positive reaction, increased osteoprotegerin(OPG) positive reaction, and decreased matrix metalloproteinase-3(MMP-3) and 8-hydroxy-2'-deoxyguanosine(8-OHdG) positivite reaction. Taken together, Bombycis Corpus increases the activity of osteoblasts, inhibits osteoclast function, promotes osteoblast function, inhibits bone tissue degradation, and inhibits bone loss due to oxidative stress. It was observed that Bombycis Corpus reduced bone loss and increased bone density caused by aging to improve male osteoporosis. Therefore, Bombycis Corpus may be used as a preventive and therapeutic agent for male osteoporosis.

Localized probiotic-guided pocket recolonization in the treatment of chronic periodontitis: a randomized controlled clinical trial

  • Kumar, Vikram;Singhal, Rameshwari;Rastogi, Pavitra;Lal, Nand;Pandey, Shivani;Mahdi, Abbas Ali
    • Journal of Periodontal and Implant Science
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    • v.51 no.3
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    • pp.199-212
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    • 2021
  • Purpose: This randomized clinical placebo-controlled trial was conducted to evaluate the effectiveness of Lactobacillus reuteri as a probiotic in guided pocket recolonization (GPR) for the treatment of chronic periodontitis (CP) adjunctive to scaling and root planing (SRP). Methods: Forty-eight CP patients were randomly assigned to 3 treatment groups: group 1 (SRP+placebo), group 2 (SRP+single application of probiotic), and group 3 (SRP+incremental application of probiotic). Clinical parameters were evaluated at baseline and at 8, 12, and 24 weeks, whereas biochemical parameters were measured at baseline and 12 weeks. Results: At 24 weeks, the probing pocket depth and clinical attachment level improved in all 3 groups from baseline with no significant intergroup differences; however, a statistically significant difference was observed in localized plaque and gingival scores between groups 1 and 3 (P<0.05). At 12 weeks, matrix metalloproteinase-8 (MMP-8), nitric oxide (NO), and gingipains-R (Rgps) levels improved in all 3 groups, with statistically significant differences between groups 1 and 3 for MMP-8 and NO (P<0.05), but no difference for Rgps levels. Conclusions: Within its limitations, the results of this study show that incremental 3-time application of L. reuteri as a probiotic led to improvements in clinical and biochemical parameters. This protocol can be a useful adjunct to SRP in the non-surgical management of CP.

Production of PMA-induced MMP-2 and MMP-9 in the HT-1080 Fibrosarcoma Cell Line is Inhibited by Corydalis heterocarpa via the MAPK-related Pathway (PMA로 자극된 HT-1080 세포에서 염주괴불주머니 추출물의 MAPK 경로를 통한 MMP-2, MMP-9 발현 억제 효과)

  • Yu, Ga Hyun;Karadeniz, Fatih;Oh, Jung Hwan;Kong, Chang-Suk
    • Journal of Life Science
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    • v.32 no.1
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    • pp.51-55
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    • 2022
  • Matrix metalloproteinase (MMP) enzymes are responsible for the degradation and formation of the extracellular matrix (ECM), and overproduction of MMPs is observed in several diseases, such as cancer and asthma, that progress with metastatic characteristics. Natural products, especially phytochemicals, have been an important source of MMP inhibitors with reduced side effects. Although the majority of phytochemicals inhibit the enzymatic activity of MMPs, some suppress MMP production. In this context, the current study evaluated the potential of Corydalis heterocarpa, a halophyte with reported bioactivities, to inhibit MMP expression in PMA-stimulated HT-1080 cells. A crude C. heterocarpa extract was shown to decrease the mRNA and protein expression of MMP-2 and MMP-9 while increasing the endogenous MMP inhibitors TIMP-1 and TIMP-2 which regulate MMP expression in healthy tissues. In addition, our results show that the inhibitory effects of C. heterocarpa might occur through suppression of the phosphorylation of MAPK signaling, the upstream activator of MMP overexpression. In conclusion, C. heterocarpa is a potential source of antimetastatic compounds that might serve as lead molecules to develop novel MMP inhibitors.

Effect of Green Tea Catechins on the Expression and Activity of MMPs and Type I Procollagen Synthesis in Human Dermal Fibroblasts (사람 섬유아세포에서 녹차 카테킨이 노화 인자인 MMP와 type 1 Procollagen 발현에 미치는 영향)

  • Shin, Hyun-Jung;Kim, Su-Nam;Kim, Jung-Ki;Lee, Byeong-Gon;Chang, Ih-Seoup
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.32 no.2 s.57
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    • pp.117-121
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    • 2006
  • Although many studies have been performed to elucidate the molecular consequence of factors that regulate skin aging, little is known about the effect of green tea catechins except EGCG. The matrix metalloproteinase (MMP), can degrade matrix proteins and results in a collagen deficiency in photodamaged skin, are known to play an important role in photoaging. This study, investigated the effects of green tea catechins on the UVA-induced MMP-1 expression, activity of MMP-2 and synthesis of type I procollagen in human dermal fibroblasts. We examined eight catechins that naturally exist in green tea leaves and compared their efficacies among them. Most of catechins inhibited the expression of MMP-1 in dose dependent manner, and the levels were reduced, especially, 57.4 and 68.2% by treatment with $1{\mu}M$ of epigallocatechin-3-gallate (EGCG) and gallocatechin-3-gallate (GCG), respectively. Also, catechins significantly suppressed the activities of MMP-2. Catechins also induced the expression of type I procollagen, however, they acted only at the concentration below $1{\mu}M$ interestingly. Furthermore, when EGCG:GCG:ECG had the ratio of 0.5:1.5:.1.3, they presented the most effective on procollagen synthesis. Therefore, we concluded that catechins significantly inhibited MMPs and induced collagen synthesis. Taken together, all these results suggested that green tea catechins might be good natural materials act as an anti-photoaging and a skin-aging improving agent.

Effects of Seaweeds on Matrix Metalloproteinases Derived from Normal Human Dermal Fibroblasts and Human Fibrosarcoma Cells (사람피부섬유아세포 및 섬유아육종세포로부터 유래된 기질금속단백질효소에 대한 해조류의 효능)

  • Park, In-Hwan;Lee, Sang-Hoon;Kim, Se-Kwon;Ngo, Dai-Nghiep;Jeon, You-Jin;Kim, Moon-Moo
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1501-1510
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    • 2011
  • In recent years novel potential pharmocological candidates have been looked for in animal, seaweed, sponge, fungi and marine bacteria resources. In this study, matrix metalloproteinases (MMPs) that play an important role in metastasis, arthritis, chronic inflammation and wrinkle formation were used as target enzymes to screen therapeutic agents. The inhibitory effects of several marine algae including green algae (5 species), red algae (18 species) and brown algae (4 species) methanolic extracts on MMPs were investigated in human dermal fibroblasts and human fibrosarcoma cell line (HT1080 cells) using gelatin zymography. In human dermal fibroblasts, the inhibition of MMP-2 was observed in Laurencia okamurae, Polysiphonia japonica, Grateloupia lanceolate and Sinkoraena lancifolia of red algae. In contrast, MMP-2 activation was enhanced in Enteromorpha compressa and E. linza of green algae, and Peltaronia bighamiae and Sargassum thunbergii of brown algae. In human fibrosarcoma cells, MMP-9 activation was decreased in the presence of S. thunbergii of brown algae, Polysiphonia japonica in red algae and E. compressa and E. linza of green algae. The interesting finding is that E. compressa and E. linza of green algae, and S. thunbergii of brown algae exhibited a positive effect on MMP-2 in normal cells, but a negative effect on MMP-9 in cancer cell lines. These results suggest that E. compressa and E. linza of green algae, and S. thunbergii of brown algae contain potential therapeutic ingredients for cancer treatment.

Effect of Graphene with Antioxidant Activity on Matrix Metalloproteinase in HT1080 Cells (항산화 활성을 가진 그래핀이 HT1080 세포에서 기질금속단백질분해효소에 미치는 영향)

  • Lee, Su-Gyeng;Kim, Moon-Moo;Oh, Yunghee
    • Journal of Life Science
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    • v.23 no.10
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    • pp.1209-1215
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    • 2013
  • Graphene is an allotrope of carbon that is composed of one-atom-thick planar sheets. It is known to have a preventive effect on cancer in photothermal therapy and a protective effect in DNA oxidation. The effect of graphene on oxidative stress and matrix metalloproteinases (MMPs) was investigated in human fibrosarcoma HT1080 cells. The results showed that graphene specifically exerted an inhibitory effect on DNA oxidation, but it did not inhibit other oxidative stress. In addition, graphene decreased the expression and the activation of MMP-2 and MMP-9 stimulated by phenazine methosulfate-m, which induces the production of intracellular hydrogen peroxide. In particular, the expression of antioxidant enzymes, such as superoxide dismutase (SOD-2), was decreased in the HT1080 cells, indicating that the decrease in the expression level of SOD was due to the antioxidant effect of graphene. These results suggest that the inhibitory effect of oxidative stress in the presence of graphene could inhibit the expression of MMPs in HT1080 cells. Based on the above results, graphene may have chemoprevention properties through inhibition of MMP-2 and MMP-9 related to metastasis.