Concentration of Serum Matrix Metalloproteinase-3 in Patients With Primary Biliary Cholangitis

Abstract

Background and AimsMetalloproteinases (MMPs) are involved in many distinct processes in the liver. Matrix metalloproteinase-3 (MMP-3) plays an important role in connective tissue remodeling, degradation of collagen (types II, III, IV, IX, and X), proteoglycans, fibronectin, laminin, and elastin. In addition, MMP-3 can also activate other MMPs such as MMP-1, MMP-7, and MMP-9. Primary biliary cholangitis (PBC) is a cholestatic, autoimmune liver disease, characterized by the progressive destruction of intrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and liver failure. Fibrosis is the result of an imbalance between production and degradation of the extracellular matrix surrounding hepatocytes. Our aim in the present study was to determine whether the measurement of serum MMP-3 is clinically useful for assessing ongoing liver fibrosis in patients with PBC.MethodsThe MMP-3 concentration was determined in 182 PBC patients and 80 non-PBC controls using a commercially available ELISA kit.ResultsHigher concentrations of MMP-3 were found in 61% of PBC patients. PBC subjects had greater MMP-3 levels than controls: 68.9 ± 62.6 vs 21.3 ± 7.4 ng/mL, p < 0.001 for healthy subjects; 68.9 ± 62.6 vs 22.7 ± 7.6 ng/mL, p = 0.022 for autoimmune hepatitis controls; and 68.9 ± 62.6 vs 37.2 ± 17.4 ng/mL, p = 0.002 for primary sclerosing cholangitis controls. The serum MMP-3 concentration was significantly elevated in patients with higher bilirubin concentration (107.6 ± 85.8 vs 61.6 ± 46.1 ng/mL, p < 0.001) and was correlated with the level of antimitochondrial antibodies specific for PBC. The concentration of MMP-3 in sera of PBC patients was also found to correlate with the state of liver fibrosis (OR = 4.3; p < 0.01).ConclusionsOur study demonstrated significantly higher MMP-3 levels in PBC patients than in healthy and pathological controls. Increased MMP-3 concentrations were positively correlated with various clinical and immunological parameters, and advanced liver fibrosis. The level of MMP-3 was associated with hepatic dysfunction and could play a role in the pathophysiology of hepatic fibrosis in PBC.

Laser Therapy Changes the Expression of Matrix Metalloproteinases in Bleomycin-Induced Skin Fibrosis

“…In 48h after the therapy, the expression of Mmp3 significantly decreases, similar to Mmp2 (Figure 3). As found earlier, stromelysin 1, encoded by Mmp3, contributes to the degradation of collagens, elastin, laminins, and other extracellular proteins [12]. In addition, stromelysin 1 activates several matrix metalloproteinases: namely interstitial collagenase/ MMP1, matrilysin/ MMP7, and gelatinase B/ MMP9, which are necessary for the degradation of proteins located in the dermal extracellular matrix [13].…”

Laser Therapy Changes the Expression of Matrix Metalloproteinases in Bleomycin-Induced Skin Fibrosis

“…Forty-eight hours after the therapy, the expression of Mmp3 significantly decreases, similar to Mmp2 ( Figure 3 ). As found earlier, stromelysin 1, encoded by Mmp3 , contributes to the degradation of collagens, elastin, laminins, and other proteins of the ECM [ 28 ]. Furthermore, stromelysin 1 activates several matrix metalloproteinases: interstitial collagenase/MMP1, matrilysin/MMP7, and gelatinase B/MMP9.…”

Enzymes of Fibrosis in Chronic Liver Disease

“…In an early study, proline hydroxylase was elevated in ten out of fourteen patients with PBC but to a lesser degree than in patients with active cirrhosis [ 62 ]. Approximately 60% of PBC patients had increased MMP-3 in serum measured by ELISA, and higher values were found in patients with advanced disease (Ludwig stage III-IV) [ 63 ]. A different research approach showed results consistent with our findings.…”