Related Experiment Video
Updated: Aug 4, 2026
Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
Published on: March 24, 2017
Serum TIMP-1, TIMP-2, and MMP-1 in patients with systemic sclerosis, primary Raynaud's phenomenon, and in normal
S A Young-Min1, C Beeton, R Laughton
1Department of Rheumatology, University of Newcastle-upon-Tyne, UK. Steven.youngMin@ncl.ac.uk
Background:
Excess tissue matrix accumulates in systemic sclerosis (SSc), accounting for both visceral and dermal fibrosis. It is suggested that decreased serum levels of matrix metalloproteinases (MMPs) or increased levels of tissue inhibitors of matrix metalloproteinases (TIMPs) may account for this matrix accumulation.
Objective:
To measure serum levels of tissue inhibitors of metalloproteinases, TIMP-1, TIMP-2, and collagenase-1 (MMP-1), in patients with diffuse cutaneous systemic sclerosis (dcSSc), limited cutaneous systemic sclerosis (lcSSc), primary Raynaud's phenomenon (RP), and in normal controls.
Methods:
Serum samples from patients with dcSSc (n=83), lcSSc (n=87), RP (n=80), and normal controls (n=98) were analysed using enzyme linked immunosorbent assays (ELISAs) for total TIMP-1, TIMP-2, and MMP-1. Results from each assay were analysed by the Kruskal-Wallis test. Dunn's multiple comparison post-test was then applied between groups.
Results:
TIMP-1 levels were significantly raised in dcSSc and lcSSc groups compared with the RP group and normal controls (p<0.01 to p<0.001). In the dcSSc group, TIMP-1 levels were significantly higher in early disease (<2 years) than in late stage disease (>4 years) (p<0.05). This was not found for the lcSSc group. Serum TIMP-2 and MMP-1 levels in dcSSc and lcSSc did not differ significantly from those in normal controls. Increased levels of TIMPs were not convincingly associated with organ disease. No assay result correlated with autoantibody status (anti-topoisomerase 1 (anti-Scl-70), anticentromere antibody, or anti-RNA polymerase). No significant differences in serum TIMP-1, TIMP-2, or MMP-1 levels were shown in the RP group compared with normal controls.
Conclusions:
Raised TIMP-1 levels in the SSc groups support the hypothesis that matrix accumulation occurs in SSc at least in part owing to decreased degradation. Moreover, the variation in TIMP-1 levels between the early and late disease stages of dcSSc seems to reflect the early progressive course of dermal fibrosis seen clinically. The expected reduction in serum MMP-1 levels in the SSc groups was not found. This suggests that tissue matrix accumulation is due to increased inhibitors rather than to decreased MMPs.
Insights
Systemic sclerosis (SSc) shows increased tissue inhibitors of metalloproteinases-1 (TIMP-1) levels, suggesting matrix accumulation is due to reduced degradation. Early diffuse cutaneous SSc has higher TIMP-1 than late stages.
Area of Science:
- Biochemistry
- Immunology
- Rheumatology
Background:
- Systemic sclerosis (SSc) is characterized by excess tissue matrix accumulation, leading to fibrosis in visceral and dermal tissues.
- This matrix buildup may result from reduced activity of matrix metalloproteinases (MMPs) or elevated levels of their inhibitors (TIMPs).
Purpose of the Study:
- To quantify serum levels of TIMP-1, TIMP-2, and MMP-1 in patients with diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and primary Raynaud's phenomenon (RP).
- To compare these levels against normal controls to understand their role in SSc pathogenesis.
Main Methods:
- Serum samples were collected from patients with dcSSc (n=83), lcSSc (n=87), RP (n=80), and healthy controls (n=98).
- Enzyme-linked immunosorbent assays (ELISAs) were used to measure total TIMP-1, TIMP-2, and MMP-1 levels.
- Statistical analysis involved the Kruskal-Wallis test and Dunn's multiple comparison post-test.
Main Results:
- TIMP-1 levels were significantly elevated in both dcSSc and lcSSc groups compared to RP and control groups (p<0.01 to p<0.001).
- In dcSSc, TIMP-1 levels were higher in early disease (<2 years) than in late disease (>4 years) (p<0.05).
- Serum TIMP-2 and MMP-1 levels did not significantly differ between SSc groups and controls; no correlation was found with organ involvement or autoantibody status.
Conclusions:
- Elevated TIMP-1 in SSc supports the hypothesis that matrix accumulation is partly due to decreased matrix degradation.
- The higher TIMP-1 in early dcSSc correlates with the clinical progression of dermal fibrosis.
- The absence of reduced MMP-1 suggests that increased inhibitors, rather than decreased MMPs, drive matrix accumulation in SSc.
More Related Videos
08:28Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
Published on: February 15, 2022
10:21Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification
Published on: September 20, 2024
