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1.
Anticancer Res ; 40(10): 5751-5756, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988902

RESUMO

BACKGROUND/AIM: A single study has shown positive association and genotype-phenotype correlation between metalloproteinase-9 (MMP-9) promoter genotypes and adult acute lymphocytic leukemia (ALL). However, there is no report about childhood ALL. Thus, this study aimed at examining the role of MMP-9 rs3918242 genotypes in childhood ALL risk. PATIENTS AND METHODS: A total of 266 childhood ALL cases and 266 healthy controls in Taiwan were examined for their MMP-9 rs3918242 genotypes via polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The MMP-9 rs3918242 CT or TT genotype carriers only had a slightly increased risk compared with CC carriers (p=0.6386 and 0.6005, respectively). The allelic frequency analysis also supported the idea that the variant T allele at MMP-9 rs3918242 is not differentially distributed between the case and control groups (p=0.4834). CONCLUSION: MMP-9 rs3918242 genotypes may indirectly influence the risk of childhood ALL. Further validations in other populations and analysis of the detail mechanisms are needed.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Metaloproteinase 9 da Matriz/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adulto , Alelos , Criança , Feminino , Genótipo , Heterozigoto , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Regiões Promotoras Genéticas/genética
2.
Medicine (Baltimore) ; 99(38): e22278, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957381

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is a multifactorial disease with gene-environment interaction resulting in progressive renal function damage. Multiple studies have assessed the association between matrix metalloproteinase-9 (MMP-9) gene promoter polymorphism and DN susceptibility. However, the results are inconclusive. In the present study, we will conduct a meta-analysis to further examine this relationship more precisely. METHODS: Electronic databases (Pubmed, Web of Science, Embase, Google Scholar, Wanfang, China Biological Medicine and China National Knowledge Infrastructure) will be used to search clinical case-control studies about MMP-9 polymorphism and DN published until 18 August 2020. The language will be restricted to Chinese and English. Two reviewers will take charge of completing the selection of study, the extraction of data as well as the assessment of study quality independently. The Newcastle-Ottawa Scale will be used to evaluate the study quality. We will evaluate the association under 5 genetic models. Fixed-effects or random-effects models will be used to calculate the effect sizes of odds ratio and 95% confidence intervals. Afterwards, subgroup analysis will be conducted in terms of the ethnicity and genotyping method. Additionally, sensitivity analysis will be performed via sequentially omitting each of the included studies one at a time. The funnel plots, Egger regression test, and Begg rank correlation test will be used to test the potential publication bias. All the statistical analyses will be performed using Review Manager 5.3 and Stata 12.0. RESULTS: This protocol reported according to the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. This study will provide a better understanding of the association between MMP-9 polymorphisms and DN risk. CONCLUSION: Publishing this protocol will minimize the potential bias related to data mining, thus contributing to generation of reliable evidence. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/H5FS4.


Assuntos
Nefropatias Diabéticas/genética , Metaloproteinase 9 da Matriz/genética , Metanálise como Assunto , Polimorfismo Genético , Revisões Sistemáticas como Assunto , Nefropatias Diabéticas/enzimologia , Predisposição Genética para Doença , Humanos , Regiões Promotoras Genéticas/genética , Fatores de Risco
3.
Gene ; 761: 145049, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32791092

RESUMO

Breast cancer (BRCA) is a highly heterogeneous disease due to the complicated microenvironment in the tumor, making the treatment benefits varied. Therefore, this study aims to identify a gene signature in the tumor microenvironment (TME) associated with the prognosis of BRCA patients. We downloaded the immune, stromal, and proliferation (ISP)-associated genes from the literature on BRCA. mRNA expression and clinical information obtained from The Cancer Genome Atlas (TCGA) were performed to identify the initial biomarker. Furthermore, we validated the robustness of the gene signature in the independent validation data set GSE20685. A four-gene signature in TME, including CD74, MMP9, RPA3, and SHCBP1, was constructed to predict the overall survival of BRCA. The survival time of the high-risk group was significantly worse than that of the low-risk group. Univariate and multivariate Cox regression analysis showed that our four-gene ISP signature was an independent prognostic factor in TCGA and GSE20685 data sets. The AUC suggested that our four-gene ISP signature was comparable to TNM classification at predicting the overall survival of BRCA patients. Interestingly, BRCA patients with high-risk scores were more likely to be associated with stromal and proliferation of cancer. In contrast, those with high-risk scores were more likely to be associated with tumor immunity-related pathway. We found an innovative biomarker in TME to predict the prognosis of BRCA. This signal might reflect the imbalance of TME and provide potential biomarkers for the individualized and precise treatment of BRCA.


Assuntos
Neoplasias da Mama/genética , Microambiente Tumoral/genética , Adulto , Antígenos CD/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Proteínas de Ligação a DNA/genética , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Haplótipos/genética , Humanos , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , Fatores de Risco , Proteínas Adaptadoras da Sinalização Shc/genética , Sialiltransferases/genética
4.
Gene ; 762: 145044, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777528

RESUMO

OBJECTIVE: Gastric cancer is the most common malignant tumor. Most patients suffering from gastric cancer die of metastasis. The role of Atrial natriuretic peptide (ANP) in inhibiting and eliminating kinds of cancer cells has been reported. Aberrant activation of Hedgehog (Hh) signaling pathway contributes to initiation and progression of various malignancies. We have previously reported that the inhibitor of Hh, cyclopamine, reduces the metastatic activity of MGC-803 via inhibiting the expression of matrix metalloproteinases (MMP)-9. It remains to be further demonstrated that ANP has the suppressive effects on invasion and metastasis in gastric cancer via Hh-mediated MMP-9 production. METHODS: Transwell, western blot, qRT-PCR were used after application of ANP on MGC-803 gastric cancer cells to determine the levels of cell migration and invasion, protein levels of MMP-9 and Hh, as well as mRNAs of MMP-9 and Hh, respectively. RESULTS: It was demonstrated that the migration and invasion were significantly lower, MMP-9 and Hh as well as their mRNAs were lower as well, in ANP-treated MGC-803 gastric cancer cells than those in control. CONCLUSIONS: The expression of MMP-9 induced by aberrant activation of Hh in MGC-803 was inhibited by ANP, which may contribute to the inhibition of cell migration and invasion. These results suggested the potential of ANP to be used in gastric cancer therapy as an inhibitor targetting Hh signaling pathway to inhibit the proliferation as well as invasion and metastasis of gastric cancer.


Assuntos
Fator Natriurético Atrial/farmacologia , Proteínas Hedgehog/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proteínas Hedgehog/genética , Humanos , Metaloproteinase 9 da Matriz/genética , Transdução de Sinais/efeitos dos fármacos
5.
Gene ; 759: 144972, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32739585

RESUMO

BACKGROUND: Numerous studies have sought associations between matrix metalloproteinase 9 (MMP-9) polymorphisms and breast cancer risk. However, these studies have yielded conflicting results. Hence, we performed an updated meta-analysis to clarify the effects of four MMP-9 gene polymorphisms (rs3918242, rs2250889, rs3787268, and rs17576) on breast cancer risk. METHODS: A comprehensive literature search for eligible studies was conducted in five electronic databases, including PubMed, Embase and Web of Science, up to March 1, 2020. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations in random-effects models. For the reduction of type I errors, a trial sequential analysis (TSA) was performed. RESULTS: Twenty-one studies (8813 breast cancer cases and 9323 controls) were included in the quantitative analysis. For rs3918242, the overall ORs were significant under allelic comparison (OR A vs. G = 1.34; 95% CI 1.03, 1.74, P = 0.028) and the recessive genetic model (OR AA vs. GG+GA = 1.40; 95% CI 1.06, 1.84, P = 0.016). For rs2250889, the ORs were significant under homozygote comparison (OR GG vs. CC = 2.57; 95% CI 1.22, 5.42, P = 0.013), heterozygote comparison (OR GC vs. CC = 2.48; 95% CI 1.17, 5.23, P = 0.018), and the dominant genetic model (OR GG+GC vs. CC = 2.53; 95% CI 1.23, 5.20, P = 0.012). No associations were observed for rs3787268 or rs17576. The subgroup analyses indicated that the risk effect of the rs3918242 A allele was observed only among Asians. TSA showed that the findings for rs3918242, rs3787268, and rs17576 were robust, but many more patients are needed before definitive conclusions can be made for rs2250889. CONCLUSION: Our meta-analysis suggests that MMP-9 rs3918242, but not rs3787268 and rs17576 polymorphisms, may be risk factors for breast cancer. The effect of rs2250889 needs further confirmation with a larger sample size.


Assuntos
Neoplasias da Mama/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Feminino , Humanos
6.
Medicine (Baltimore) ; 99(31): e21479, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756173

RESUMO

BACKGROUND: To comprehensively evaluate the association between the polymorphism of matrix metalloproteinase-9 (MMP-9)-C1562T (rs3918242) and susceptibility to chronic obstructive pulmonary disease (COPD) in middle-aged and elderly patients through Meta-analysis. METHODS: PubMed, EMBASE, CNKI, Wanfang, VIP, and other databases were searched by computer in the inception to August 2019 to collect all the case-control studies that met the inclusion criteria in this literature. Meta-analysis was performed using Stata 15.0, including the OR value calculations of the association between the merged MMP-9-C1562T polymorphism and the COPD susceptibility. Subgroup analysis, sensitivity analysis, and publication bias test were also performed. A total of 13 literature were included in this Meta-analysis with a total of 2512 cases and 2716 controls. RESULTS: The results have shown that the OR of MMP-9-C1562T T allele to C allele was 0.35 (95% confidence interval [CI]: 0.23-0.52, P < .01). The subgroup analysis of ethnicity result showed that the merged OR of MMP-9-C1562T T allele to C allele was 0.24 (95% CI: 0.17-0.34, P < .01) in Caucasian while the merged OR was 0.62 (95% CI: 0.22-1.70, P > .05) in Asian. However, there were no statistically significant models in the dominant, recessive, homozygote and heterozygote genetic models. CONCLUSION: The MMP-9-C1562T polymorphism was associated with the susceptibility to middle-aged and elderly COPD patients. Compared with T allele, C allele increased the risk of disease, especially in Caucasian, but not found in Asian.


Assuntos
Predisposição Genética para Doença/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
7.
Anticancer Res ; 40(7): 3619-3631, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620601

RESUMO

MMP-2 and MMP-9 genes have been suggested to play a role in breast cancer. Their functions have been associated with invasion and metastasis of breast cancer; however, their involvement in the development of the disease is not well-established. Herein, we reviewed the literature investigating the association between circulating levels and polymorphisms of MMP-2 and MMP-9 and breast cancer risk. Various studies report conflicting results regarding the relationship of polymorphisms in MMP-2 and MMP-9 and breast cancer risk. Nevertheless, it appears that the T allele in rs243865 and rs2285053 in MMP-2 are associated with reduced risk of breast cancer. In addition, high levels of latent form and low levels of active form of MMP-2 were observed in breast cancer patients compared to controls. For MMP-9, high latent levels and low total levels were found in breast cancer patients compared to controls. Additional studies are needed to comprehend the role of these genes in breast carcinogenesis.


Assuntos
Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo Genético/fisiologia , Alelos , Feminino , Humanos , Risco
8.
J Cancer Res Ther ; 16(3): 517-520, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719260

RESUMO

Aim of the Study: Both matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) is involved in degradation of extracellular matrix and found to stimulate invasion and metastasis in cancer patients. However, studies on the stage-specific expression of MMPs at different stages of larynx carcinoma are still lacking. In the present study, we compare the expression level of MMP-2 and MMP-9 at different stages of laryngeal carcinoma. Material and Methods: Tumor tissues samples were taken from larynx cancer patients by deep biopsy during direct laryngoscopy. Gene expression for MMP-2 and MMP-9 was analyzed using RT-PCR. Results: Significantly high expression of MMP-2 was observed compared to the MMP-9 at stage IV compared to the less advanced stages of the disease. Conclusion: Present study concluded that the MMP-2 expressed with a greater magnitude as compared to the MMP-9 in advance stages of laryngeal carcinoma.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Laríngeas/patologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Adulto , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirurgia , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/genética , Adulto Jovem
9.
Anticancer Res ; 40(8): 4523-4527, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727782

RESUMO

BACKGROUND/AIM: The studies about the roles of matrix metalloproteinases (MMPs) in pterygium diagnosis and/or prognosis are mainly based on their mRNA and protein levels, while the genomic roles of MMPs are seldom examined. The aim of this study was to investigate the contribution of MMP-9 genotypes to pterygium risk. MATERIALS AND METHODS: MMP-9 rs3918242 was genotyped in 134 pterygium cases and 268 controls via polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The rs3918242 genotype percentages of CC, CT, and TT were 73.1, 25.4 and 1.5% among cases and 74.6, 23.1 and 2.3% among controls (p trend=0.7928). The odds ratios after adjusting for age and gender for CT and TT genotypes at rs3918242 were 1.08 and 0.92 (95%CI=0.66-1.73 and 0.45-2.89, p=0.6478 and 0.6389), respectively. In addition, allelic frequency analysis showed no significant difference in the distribution of allelic frequencies between the pterygium and control groups. CONCLUSION: The genotypes at MMP-9 rs3918242 play a minor role in determining personal susceptibility to pterygium.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Pterígio/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Pterígio/diagnóstico , Taiwan
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(7): 1018-1022, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32701246

RESUMO

OBJECTIVE: To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury. METHODS: Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 µg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting. RESULTS: Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury (P < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury (P < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury (P < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma (P < 0.05) and increased further at 2 days (P < 0.01); the water content of the brain did not change significantly at 2 h (P > 0.05) but increased significantly 2 d after the injury (P < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma (P < 0.01). CONCLUSIONS: Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.


Assuntos
Edema Encefálico , Lesões Encefálicas Traumáticas , Regulação Enzimológica da Expressão Gênica , Sistema de Sinalização das MAP Quinases , Metaloproteinase 9 da Matriz , Animais , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Indazóis/farmacologia , Indazóis/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 9 da Matriz/genética , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
11.
Immunol Med ; 43(3): 121-129, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32546118

RESUMO

The roles of interleukin-22 (IL-22) in carcinogenesis have been proposed in various neoplasms. Increased expression of IL-22 has been observed in oral squamous cell carcinoma (OSCC) lesions as well as in other cancers. OSCC is still associated with poor prognosis and a high mortality rate because of its invasiveness and frequent lymph node metastasis. In the present study, we investigated the effects of IL-22 on OSCC cells. The human OSCC cell lines Ca9-22 and SAS were stimulated with IL-22 (1-10 ng/mL), and their migration abilities were examined using a cell scratch assay. A Matrigel invasion assay was performed to evaluate the invasion abilities of OSCC cells. Signal transducer and activator of transcription 3 (STAT3) phosphorylation, matrix metalloproteinase (MMP) and epithelial-mesenchymal transition (EMT)-related genes and proteins were also examined. IL-22 treatment promoted the migration and invasion abilities of OSCC cells without increasing their viability. IL-22 stimulation also induced STAT3 phosphorylation, MMP-9 activity and EMT-related genes and proteins. Our findings suggest that IL-22 has possible roles in the development of OSCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Movimento Celular/efeitos dos fármacos , Interleucinas/efeitos adversos , Interleucinas/fisiologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Humanos , Metástase Linfática/genética , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Invasividade Neoplásica/genética , Fosforilação/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
12.
Invest Ophthalmol Vis Sci ; 61(5): 29, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32421147

RESUMO

Purpose: Matrix metalloproteinases (MMPs) are involved in extracellular matrix (ECM) maintenance and remodeling. The present study aimed to determine whether transforming growth factor (TGF)-ß2 regulates MMP-2 and MMP-9 levels and activities in astrocytes derived from the optic nerve head (ONH) and the role of statins in such modulation. Methods: Primary astrocytes cultured from the lamina cribrosa of human donor ONHs were incubated with three types of statins (5 µg/mL) for 1 hour followed by recombinant TGF-ß2 (5 ng/mL) for various periods to test their effects. Levels and activities of MMP-2 and MMP-9 in astrocytes in vitro were determined by western blotting and zymography, respectively. Levels of phosphorylated myosin phosphatase target subunit 1 (MYPT1) in astrocyte lysates were determined by western blotting, and those of phosphorylated myosin light chain (MLC) were determined by western blotting and immunocytochemistry. Results: MMP-2 and MMP-9 levels were upregulated by TGF-ß2 in human ONH astrocytes. Prior incubation with simvastatin, lovastatin, and atorvastatin inhibited TGF-ß2-mediated MMP-2 and MMP-9 expression and activities. Prior incubation with statins downregulated the TGF-ß2-induced phosphorylation of MYPT1 and MLC, which are downstream substrates of RhoA and ROCKs. Conclusions: Statins inhibited the TGF-ß2-mediated regulation of MMP-2 and MMP-9 by inhibiting the RhoA/ROCK signaling pathway. Considering the role of MMP in ECM remodeling, the present findings support the notion that statins positively impact ECM remodeling within the ONH.


Assuntos
Astrócitos/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/fisiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Fator de Crescimento Transformador beta2/antagonistas & inibidores , Quinases Associadas a rho/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores , Adulto , Astrócitos/enzimologia , Atorvastatina/farmacologia , Western Blotting , Células Cultivadas , Feminino , Humanos , Imuno-Histoquímica , Lovastatina/farmacologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Fosfatase de Miosina-de-Cadeia-Leve/metabolismo , Disco Óptico/citologia , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Sinvastatina/farmacologia , Fator de Crescimento Transformador beta2/farmacologia
13.
BMC Neurol ; 20(1): 218, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32471473

RESUMO

BACKGROUND: Several studies have reported the association between polymorphisms in Matrix metalloproteinases (MMPs) gene family and risk of Multiple sclerosis (MS). However, the results have been inconsistent and inconclusive. To resolve this issue, here we performed a systematic review and meta-analysis of the MMP-91562 C/T (rs3918242), MMP-3 (- 1612 5A/6A), and MMP-2 (- 1306 C/T) polymorphisms and susceptibility to MS. METHODS: We conducted a comprehensive systematic search in the major electronic database, including Scopus and PubMed to look up for relevant studies published before December 2019 that surveyed the association between the MMP-91562 C/T (rs3918242), MMP-3 (- 1612 5A/6A), and MMP-2 (- 1306 C/T) polymorphisms and susceptibility to MS. The level of association between the polymorphisms and susceptibility to MS in the polled analysis was determined by calculating the odds ratio (OR) and the corresponding 95% confidence interval (CI). RESULTS: We found 15 studies containing 2430 MS subjects and 2304 controls. A statistically significant association was observed in the all five comparisons of the MMP-91562 C/T polymorphism and MS risk as follows: dominant model (OR = 1.62, 95% CI = 1.03-2.53, P = 0.03), recessive model (OR = 2.69, 95% CI = 1.68-4.29, P < 0.001), allelic model (OR = 1.51, 95% CI = 1-2.28, P = 0.04), TT vs. CC model (OR = 3.20, 95% CI = 1.87-5.46, P < 0.001), and CT vs. CC model (OR = 1.53, 95% CI = 1.02-2.28, P = 0.04). CONCLUSIONS: Our meta-analysis revealed significant association of MMP-9 (- 1562 C/T) Single-nucleotide polymorphism (SNP) with MS susceptibility that increased the disease risk.


Assuntos
Predisposição Genética para Doença , Metaloproteinase 9 da Matriz/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único/genética , Humanos , Masculino , Metaloproteinases da Matriz/genética , Razão de Chances
14.
Anim Sci J ; 91(1): e13350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219980

RESUMO

This study investigated the effect of type-I interferon (IFN) on the expression of matrix metalloproteinases (MMPs) of the bovine endometrial stromal cells (BES) and epithelial cells (BEE). The cells were separated and purified from the caruncles and cultured in DMEM/F-12 containing 10% fetal bovine serum. Spheroids were generated by using ascorbate. Zymograms of the supernatant showed that BEE predominantly expressed MMP-9, whereas MMP-2 was expressed in BES and homo-spheroids. While MMPs expression was not detected in hetero-spheroids. Real-time quantitative PCR revealed that type-I IFN and P4 suppressed the gene expression of MMP-2 and MMP-9 in hetero-spheroids, respectively. On the other hand, gelatin zymography analysis of the supernatant showed that type-I IFN strongly promote the clearance of MMPs. While zymograms of the MMPs stocked in the hetero-spheroids were significantly reduced by type-I IFN. Phenylmethanesulfonyl fluoride and leupeptin (both are serine proteinase inhibitors) significantly repressed the clearance of MMP-2 and MMP-9 induced by type-I IFN. Moreover, collagen fibers in hetero-spheroids significantly decreased after the treatment with type-I IFN. In conclusion, it was suggested that type-I IFN participate in the tissue remodeling by regulation the clearance of MMPs.


Assuntos
Bovinos/metabolismo , Endométrio/citologia , Endométrio/metabolismo , Expressão Gênica/efeitos dos fármacos , Interferon Tipo I/farmacologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Células Estromais/metabolismo , Animais , Células Cultivadas , Feminino , Humanos , Gravidez
15.
Hum Cell ; 33(3): 512-520, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32130677

RESUMO

Pre-eclampsia (PE) is a disorder of pregnancy characterized by proteinuria and high blood pressure, affecting 2-8% of pregnancies worldwide. Previous studies have shown that PE is closely associated with trophoblast cell dysfunction. Here, we investigated the role of tissue factor pathway inhibitor-2 (TFPI-2) in regulating the biological processes of trophoblast cells. The TFPI-2 levels in plasma samples and placental tissues were tested by ELISA, immunohistochemistry, qRT-PCR, and western blot. HTR8/Svneo cell line was used to simulate the primary trophoblast cells and H/R culture was applied to mimic the oxidative stress state of PE. MTT assay, Annexin V/propidium iodide (PI) apoptosis assay, and transwell assay were used to determine the cell proliferation, apoptosis, and invasion. The expression levels of matrix metalloproteinases (MMPs) were evaluated by western blot. The expression of TFPI-2 was remarkably up-regulated in both the serum and placenta of PE patients. Hypoxia/reoxygenation increased the expression of TFPI-2 in HTR-8/SVneo cell line. TFPI-2 promoted that cell proliferation and inhibited the cell apoptosis of HTR8/SVneo cells in H/R condition. In addition, downregulation of TFPI-2 increased the cell invasion and the expression of MMP2 and MMP9. This study reveals that TFPI-2 plays a crucial role in monitoring the biological function of trophoblast cells, which might provide theoretical basis and therapeutic targets for the treatment of PE.


Assuntos
Proliferação de Células/genética , Glicoproteínas/fisiologia , Pré-Eclâmpsia/patologia , Trofoblastos/patologia , Células Cultivadas , Feminino , Expressão Gênica/genética , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Terapia de Alvo Molecular , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/terapia , Gravidez , Regulação para Cima/genética
16.
Medicine (Baltimore) ; 99(9): e19394, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118792

RESUMO

This study aimed to investigate the expression of c-Fos and matrix metallopeptidase 9 (MMP-9) in dental pulp of patients receiving orthodontic treatment via wire appliance.Fifteen patients (30 teeth in total) were randomly assigned to five groups: t = 0, t = 1, t = 4, t = 8 and t = 12 (n = 6). The first maxillary premolars of patients in the t = 0 group were extracted without any orthodontic treatment. An intrusive force of 300 g was applied on first maxillary premolars in the other four groups via wire appliances. This force was maintained for 1 week for t = 1 group, 4 weeks for t = 4 group, 8 weeks for t = 8 group, or 12 weeks for t = 12 group, before the teeth were extracted.The expression of c-Fos and MMP-9 in the pulps of each group was analyzed by immunohistochemical staining and real-time PCR. The relationship in the protein expression between c-Fos and MMP-9 in the dental pulp was analyzed by Pearson correlation analysis.Intrusive force of 300 g increased the expression of both c-Fos and MMP-9 in the dental pulp. The protein expression of MMP-9 in the dental pulp was significantly correlated with the expression of c-Fos (P < .001).Extreme intrusive force upregulates c-Fos and MMP-9 expression in the dental pulp. Moreover, protein expression of c-Fos and MMP-9 is significantly correlated under intrusive force.


Assuntos
Polpa Dentária/lesões , Metaloproteinase 9 da Matriz/análise , Proteínas Proto-Oncogênicas c-fos/análise , Estresse Mecânico , Adulto , Análise de Variância , China , Polpa Dentária/patologia , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/genética , Proteínas Proto-Oncogênicas c-fos/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos
17.
Z Naturforsch C J Biosci ; 75(3-4): 113-120, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32191627

RESUMO

Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are very important gelatinases that are overexpressed during tumor metastasis. Up to date, several MMP inhibitors have been developed from natural sources as well as organic synthesis. In the present study, the MMP-2 and MMP-9 inhibitory effects of 3,5-dicaffeoyl-epi-quinic acid (DCEQA), a caffeoylquinic acid derivative isolated from Atriplex gmelinii, were investigated in phorbol 12-myristate 13-acetate (PMA)-treated human HT1080 fibrosarcoma cells. Gelatin zymography and immunoblotting showed that DCEQA significantly inhibited the PMA-induced activation and expression of MMP-9 but was not able to show any effect against MMP-2. DCEQA treatment was also shown to upregulate the protein expression of tissue inhibitor of MMP-1 along with decreased MMP-9 protein levels. Moreover, the effect of DCEQA on phosphorylation of mitogen activated protein kinases (MAPKs), analyzed by immunoblotting, indicated the DCEQA inhibited the MMP-9 by downregulation of MAPK pathway. Collectively, current results suggested that DCEQA is a potent MMP-9 inhibitor and can be utilized as lead compound for treatment of pathological complications involving enhanced MMP activity such as cancer metastasis.


Assuntos
Atriplex/química , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Ésteres de Forbol/efeitos adversos , Ácido Quínico/análogos & derivados , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Estrutura Molecular , Extratos Vegetais/química , Ácido Quínico/química , Ácido Quínico/farmacologia
18.
J Genet ; 992020.
Artigo em Inglês | MEDLINE | ID: mdl-32089521

RESUMO

Novel approaches to preterm births are underway building upon our prior discoveries and probing into unknown discovery pathways. The recent findings showed a high affinity of MMP-9 in serum and its polymorphisms for preterm birth. This study, which is a hospital-based case-control study, aims to investigate the association of MMP-1, MMP-8 and MMP-9 polymorphisms, and levels of MMP-9 in preterm birth. Increased level of MMP-9 was reported in cases as compared to control. The significant association of MMP-9 (-1562) CT (P = 0.001; OR = 1.44(CI = 0.97-2.14)) and TTgenotype (P = 0.05;OR = 2.6 (CI = 1.46-4.69)) were reported in preterm birth. Our findings suggest that the MMP-9 plays an important role in contributing preterm labour and this can be used as a diagnostic tool during pregnancy.


Assuntos
Estudos de Associação Genética , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 8 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo Genético , Nascimento Prematuro/etiologia , Adulto , Alelos , Estudos de Casos e Controles , Genótipo , Haplótipos , Humanos , Razão de Chances , Adulto Jovem
19.
Life Sci ; 248: 117445, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32081664

RESUMO

AIMS: Atherosclerosis (AS) is a common cardiovascular disease with complicated pathogenesis. Long non-coding RNAs (lncRNAs) have been reported to be associated with AS progression. We aimed to explore the role and underlying mechanism of HOXA transcript at the distal tip (HOTTIP) in AS. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of HOTTIP, miR-490-3p and high mobility group B 1 (HMGB1) in AS patients' sera and oxidized low-density lipoprotein (ox-LDL) induced human aortic vascular smooth muscle cells (HA-VSMCs). Cell Counting Kit-8 (CCK-8) assay and transwell assay were conducted to evaluate the proliferation and migration of HA-VSMCs, respectively. Western blot assay was carried out to determine the levels of proliferating cell nuclear antigen (PCNA), matrix metalloprotein 2 (MMP2), MMP9 and HMGB1. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to verify the targeting association between HOTTIP and miR-490-3p, as well as miR-490-3p and HMGB1. KEY FINDINGS: HOTTIP and HMGB1 were upregulated and miR-490-3p was downregulated in the sera of AS patients and ox-LDL-stimulated HA-VSMCs. HOTTIP knockdown suppressed ox-LDL induced proliferation and migration in HA-VSMCs. MiR-490-3p was identified as a target of HOTTIP and HOTTIP overexpression abolished the inhibition on cell proliferation and migration mediated by miR-490-3p in ox-LDL-induced HA-VSMCs. Moreover, miR-490-3p inhibition promoted cell proliferation and migration by directly targeting HMGB1 in ox-LDL-induced HA-VSMCs. Besides, HOTTIP knockdown repressed the activation of PI3K-AKT signaling pathway. SIGNIFICANCE: HOTTIP knockdown suppressed cell proliferation and migration by regulating miR-490-3p/HMGB1 axis and PI3K-AKT pathway in ox-LDL-induced HA-VSMCs.


Assuntos
Aterosclerose/genética , Proteína HMGB1/genética , MicroRNAs/genética , Miócitos de Músculo Liso/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , Aorta/metabolismo , Aorta/patologia , Aterosclerose/sangue , Aterosclerose/patologia , Estudos de Casos e Controles , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica , Proteína HMGB1/metabolismo , Humanos , Lipoproteínas LDL/farmacologia , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
20.
Curr Pharm Biotechnol ; 21(9): 862-871, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32081107

RESUMO

BACKGROUND AND OBJECTIVE: Dental peri-implantitis, which can be caused by several different microbial factors, is characterized by inflammatory lesions of the surrounding hard and soft tissues of an oral implant. Matrix Metalloproteinase 9 (MMP9) is thought to be involved in the pathogenesis of peri-implantitis. However, the regulatory mechanism of MMP9 in peri-implantitis has not been fully elucidated. In this study, we tried to evaluate the regulatory mechanism of MMP9 in peri-implantitis. METHODS: We collected Peri-Implant Crevicular Fluid (PICF) from ten healthy implants and ten periimplantitis patients and compared their expression level of MMP9. We also cultured macrophages from the peripheral blood of healthy volunteers infected by Porphyromonas gingivalis to reveal the regulatory mechanism of MMP9 in peri-implantitis. Western blot, immunofluorescence staining and quantitative Polymerase Chain Reaction (RT-PCR) were used to better characterize the mechanism of MMP9. RESULTS: The expression of MMP9 was up-regulated in peri-implantitis patient PICF and P. gingivalis infected human macrophages. LOX-1, not dectin-1, was found to mediate MMP9 expression in human macrophages with P. gingivalis infection. Expression of Erk1/2 was responsible for infection-induced MMP9 expression. Finally, use of a broad-spectrum metalloproteinase inhibitor impaired LOX-1 expression in infected macrophages. CONCLUSION: Our results demonstrate that MMP9 is involved in dental peri-implantitis and is regulated by LOX-1 and Erk1/2. This LOX-1/MMP9 signaling pathway may represent a potential drug target for peri-implantitis.


Assuntos
Implantes Dentários , Sistema de Sinalização das MAP Quinases/genética , Macrófagos/metabolismo , Metaloproteinase 9 da Matriz/genética , Peri-Implantite/metabolismo , Receptores Depuradores Classe E/metabolismo , Humanos , Macrófagos/microbiologia , Masculino , Peri-Implantite/etiologia , Porphyromonas gingivalis/crescimento & desenvolvimento , Regulação para Cima
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