更新于：2024-11-01

MMP13 x MMP8 x MMP2 x MMP9

更新于：2024-11-01

基本信息

关联

项与 MMP13 x MMP8 x MMP2 x MMP9 相关的药物

RS-113456

靶点

MMP13 x MMP2 x MMP8 x MMP9

作用机制

MMP13抑制剂 [+3]

在研机构-

原研机构

Roche Palo Alto LLC

在研适应症-

非在研适应症

关节炎 [+1]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 MMP13 x MMP8 x MMP2 x MMP9 相关的临床结果

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100 项与 MMP13 x MMP8 x MMP2 x MMP9 相关的转化医学

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0 项与 MMP13 x MMP8 x MMP2 x MMP9 相关的专利（医药）

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134

项与 MMP13 x MMP8 x MMP2 x MMP9 相关的文献（医药）

2024-08-01·Annals of Vascular Surgery

Matrix Metalloproteinase and Aortic Aneurysm: A Two-sample Mendelian Randomization Study

Article

作者: Li, Meijun ; Qin, Tao ; Li, Pinglan ; Zhang, Guangjun ; Liang, Jianlin ; Zhong, Jiankai

BACKGROUNDStudies have linked matrix metalloproteinases (MMPs) to both thoracic aortic aneurysm and abdominal aortic aneurysm (TAA and AAA). The precise MMPs entailed in this procedure, however, were still unknown. This study used a two-sample Mendelian randomization (MR) analysis to look into the causal relationship between MMPs and the risk of TAA and AAA.METHODSEight MMPs, including MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-12, and MMP-13, were found among people of European ancestry with accessible Genome-Wide Association Studies (GWAS). We employed the findings from Genome-Wide Association Studies (GWAS) for 8 MMPs, and TAA and AAA from the FinnGen consortiums (3,201 cases and 317,899 controls, respectively) were used in a two-sample MR analysis. The primary method of analysis for MR was the inverse variance weighted (IVW) method, along with analyses of heterogeneity and horizontal pleiotropy. 31 single-nucleotide polymorphisms connected to MMP were retrieved.RESULTSIVW demonstrated a negative causal association between TAA and AAA and serum MMP-12 levels. The incidence of TAA decreased by 1.031% for every 1 ng/mL increase in serum MMP-12 [odds ratio (OR) = 0.897, 95% confidence interval (CI): 0.831-0.968, P = 0.005]. The incidence of AAA fell by 1.653% (OR = 0.835, 95% CI: 0.752-0.926, P = 0.001) for every 1 ng/mL increase in serum MMP-12. There was no horizontal pleiotropy or heterogeneity in the MR data (P > 0.05).CONCLUSIONSThe levels of TAA and AAA and serum MMP-12 are causally related. MMP-12 is a factor that reduces the risk of AAA and TTA. Our study suggested that MMP-12 level is causally associated with a decreased risk of TAA and AAA.

2024-03-01·Biochimie

Matrix metalloproteinase landscape in the imiquimod-induced skin inflammation mouse model

Article

作者: Koch, Janne ; Petersson, Karsten ; Savickas, Simonas ; Heinz, Andrea ; Canbay, Vahap ; Malmsten, Martin ; Noddeland, Heidi Kyung ; Jensen, Louise Bastholm ; Auf dem Keller, Ulrich ; Lind, Marianne

Inflammation and autoimmunity are known as central processes in many skin diseases, including psoriasis. It is therefore important to develop pre-clinical models that describe disease-related aspects to enable testing of pharmaceutical drug candidates and formulations. A widely accepted pre-clinical model of psoriasis is the imiquimod (IMQ)-induced skin inflammation mouse model, where topically applied IMQ provokes local skin inflammation. In this study, we investigated the abundance of a subset of matrix metalloproteinases (MMPs) in skin from mice with IMQ-induced skin inflammation and skin from naïve mice using targeted proteomics. Our findings reveal a significant increase in the abundance of MMP-2, MMP-7, MMP-8, and MMP-13 after treatment with IMQ compared to the control skin, while MMP-3, MMP-9, and MMP-10 were exclusively detected in the IMQ-treated skin. The increased abundance and broader representation of MMPs in the IMQ-treated skin provide valuable insight into the pathophysiology of skin inflammation in the IMQ model, adding to previous studies on cytokine levels using conventional immunochemical methods. Specifically, the changes in the MMP profiles observed in the IMQ-treated skin resemble the MMP patterns found in skin lesions of individuals with psoriasis. Ultimately, the differences in MMP abundance under IMQ-induced inflammation as compared to non-inflamed control skin can be exploited as a model to investigate drug efficacy or performance of drug delivery systems.

2023-12-01·CARTILAGE

Is the Synovium the First Responder to Posttraumatic Knee Joint Stress? The Molecular Pathogenesis of Traumatic Cartilage Degeneration

Article

作者: Elphingstone, Joseph ; Kwapisz, Adam ; Herman, Katarzyna ; Synder, Marek ; Szemraj, Janusz ; Piwnik, Marcin ; Momaya, Amit ; Grzegorzewski, Andrzej

Objective The aim of this study was to evaluate if a similar catabolic and inflammatory gene pattern exists between the synovium, hyaline cartilage, and blood of patients with the knee joint tissues and if one precedes the other. Design A total of fifty-eight patients (34 females and 24 males) with a mean age of 44.7 years (range, 18-75) underwent elective knee arthroscopy due to previously diagnosed pathology. Full blood samples were collected preoperatively from synovium and cartilage samples intraoperatively. Real time PCR with spectrophotometric analysis was performed. Following genes taking part in ECM (extracellular matrix) remodeling were selected for analysis: MMP-1, MMP-2, MMP-8, MMP-9, MMP-13, MMP-14, ADAMTS-4 (Agg1) and ADAMTS-5 (Agg2) proteases, TIMP-1, and TIMP-2 – their inhibitors - and IL-1 and TNF-α cytokines. Results Analysis revealed a strong and significant correlation between gene expression in synovial and systemic blood cells (p <0.05 for all studied genes) with ADAMTS-4, ADAMTS-5, IL-1, TNF-α and TIMP-2 expression most positively correlated with an R>0.8 for each. An analysis between chondrocytes and systemic blood gene expression shown no significant correlation for all genes. Bivariate correlation of International Cartilage Repair Society grading and genes expression revealed significant associations with synovial MMP-1, MMP-2, MMP-8, MMP-9, IL-1, TNF-α and TIMP-2. Conclusion We suggest that the synovial tissue is the first responder for knee joint stress factors in correlation with the response of blood cells. The chondrocyte’s genetic response must be further investigated to elucidate the genetic program of synovial joints, as an organ, during OA development and progression.