Structural Basis of the Matrix Metalloproteinases and Their Physiological Inhibitors, the Tissue Inhibitors of Metalloproteinases

Diabetes mellitus types 1 and 2 are chronic diseases that cause serious health complications, including dermatologic problems. The diabetic skin is characterized by disturbances in collagen metabolism. A tissue remodeling depends on the degradation of extracellular matrix through the matrix metalloproteinases, which are regulated by e.g. the tissue inhibitors of metalloproteinases. The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is essential to maintain homeostasis in the skin. The aim of this study was to determine the concentration of metalloproteinase 2, tissue inhibitor of metalloproteinase 3 and the concentration of collagen type 1 in unwounded skin of diabetes type 1 and 2 and healthy controls. The treatment of diabetes resulted in a significant decrease of MMP2, increase of TIMP3 and COL1 concentrations in the skin as compared to the untreated diabetic skin. The concentrations of MMP2 in the skin of treated rats did not show significant differences from the healthy control group. TIMP3 concentrations in the skin of treated rats are not returned to the level observed in the control group. Disturbances of the extracellular matrix of the skin are similar in diabetes type 1 and 2. Application of insulin in diabetes therapy more preferably affects the extracellular matrix homeostasis of the skin.

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Structural Basis of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases

Molecular Biotechnology ◽

10.1385/mb:25:3:241 ◽

2003 ◽

Vol 25 (3) ◽

pp. 241-266 ◽

Cited By ~ 74

Author(s):

Klaus Maskos ◽

Wolfram Bode

Keyword(s):

Matrix Metalloproteinases ◽

Tissue Inhibitors Of Metalloproteinases ◽

Structural Basis ◽

Tissue Inhibitors

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MMP-10, MMP-7, TIMP-1 and TIMP-2 mRNA expression in esophageal cancer

Acta Biochimica Polonica ◽

10.18388/abp.2016_1408 ◽

2017 ◽

Vol 64 (2) ◽

Cited By ~ 4

Author(s):

Agnieszka Juchniewicz ◽

Oksana Kowalczuk ◽

Robert Milewski ◽

Wojciech Laudański ◽

Piotr Dzięgielewski ◽

...

Keyword(s):

Esophageal Cancer ◽

Matrix Metalloproteinases ◽

Mrna Expression ◽

Tissue Inhibitors Of Metalloproteinases ◽

Clinicopathologic Features ◽

Tumour Stage ◽

Rt Pcr ◽

Tissue Inhibitors ◽

Node Metastasis ◽

The Matrix

Introduction: Tissue inhibitors of metalloproteinases (TIMP) and the matrix metalloproteinases (MMP) are involved in the spread of cancer. Methods: We have evaluated the matrix metalloproteinases’ (MMP-10, MMP-7) and their inhibitors’ (tissue inhibitors of metalloproteinases – TIMP-1, TIMP-2) mRNA expression in 61 esophageal cancer samples from patients who had undergone surgery, by using real-time quantitative RT-PCR, and correlated the results with the patient clinicopathologic features. Results: MMP-10, MMP-7, TIMP-1, TIMP-2 were overexpressed in 73%, 85%, 55% and 42% of esophageal cancer samples, respectively. The expression of MMP-10, TIMP-1, and TIMP-2 correlated with the tumor size. The MMP-7 overexpression was associated with the tumour stage (I, II vs III, p=0.05) and lymph node metastasis (N0 vs N1, p=0.037). Conclusions: We conclude that in the resected esophageal cancer an increased mRNA expression of MMP-7, MMP-10 and TIMP-1 correlated with clinicopathologic features. We suggest that these genes may play a role during progression of the disease.

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Detection of the Matrix Metalloproteinases MMP-2 and MMP-9 and Tissue Inhibitors of Metalloproteinases TIMP-1 and TIMP-2 in Llama (Lama glama) Oviduct

Reproduction in Domestic Animals ◽

10.1111/rda.12317 ◽

2014 ◽

Vol 49 (3) ◽

pp. 492-498 ◽

Cited By ~ 8

Author(s):

R Zampini ◽

ME Argañaraz ◽

DC Miceli ◽

SA Apichela

Keyword(s):

Matrix Metalloproteinases ◽

Tissue Inhibitors Of Metalloproteinases ◽

Tissue Inhibitors ◽

The Matrix ◽

Lama Glama

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Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors

Biochemical Society Symposium ◽

10.1042/bss0700201 ◽

2003 ◽

Vol 70 ◽

pp. 201-212 ◽

Cited By ~ 51

Author(s):

Hideaki Nagase ◽

Keith Brew

Keyword(s):

Three Dimensional ◽

Therapeutic Interventions ◽

Tissue Inhibitors Of Metalloproteinases ◽

Structural Basis ◽

Structural Elements ◽

Ridge Structure ◽

Extracellular Matrix Components ◽

Metalloproteinase Inhibitors ◽

The Matrix ◽

A Disintegrin And Metalloproteinase

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases.

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