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Decrease in matrix metalloproteinase‑3 activity in systemic sclerosis fibroblasts causes α2‑antiplasmin and
Hirofumi Niwa1, Yosuke Kanno1, En Shu1
1Department of Dermatology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan.
Molecular Medicine Reports
|September 18, 2020
Summary
Matrix metalloproteinase-3 (MMP-3) degrades alpha2-antiplasmin (α2AP) in systemic sclerosis (SSc) fibroblasts, reducing fibrosis markers. This suggests MMP-3 as a potential therapeutic for SSc by targeting α2AP and extracellular matrix components.
Area of Science:
- Rheumatology and Immunology
- Molecular Biology
- Biochemistry
Background:
- Systemic sclerosis (SSc) is an autoimmune disease causing fibrosis, with elevated alpha2-antiplasmin (α2AP) expression in SSc dermal fibroblasts linked to fibrosis progression.
- Matrix metalloproteinase-3 (MMP-3) is an extracellular matrix (ECM)-degrading enzyme, and its interaction with α2AP in SSc is not fully understood.
Purpose of the Study:
- To investigate the relationship between α2AP and MMP-3 in systemic sclerosis (SSc).
- To evaluate the effect of MMP-3 on α2AP and fibrotic markers in SSc fibroblasts.
Main Methods:
- Serum levels of α2AP and MMP-3 were measured in SSc patients and healthy controls via ELISA.
- α2AP, MMP-3, and TIMP-1 expression in normal and SSc fibroblasts were analyzed using western blotting.
- Recombinant α2AP and MMP-3 were used to treat normal and SSc fibroblasts to assess effects on α-SMA and type I collagen.
Main Results:
- Serum levels of α2AP and MMP-3 did not differ significantly between SSc patients and controls.
- SSc fibroblasts showed increased α2AP expression and a decreased MMP-3/TIMP-1 ratio.
- MMP-3 degraded α2AP, and its stimulation of SSc fibroblasts reduced α2AP, α-SMA, and type I collagen, reversing the pro-fibrotic phenotype.
Conclusions:
- MMP-3 attenuates fibrosis progression in SSc by degrading α2AP and ECM components.
- MMP-3 demonstrates potential as a novel therapeutic agent for treating systemic sclerosis.
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