Interleukin-1β upregulates matrix metalloproteinase-13 gene expression via c-Jun N-terminal kinase and p38 MAPK pathways in rat hepatic stellate cells

• Published in: Molecular medicine reports Vol. 8; no. 6; pp. 1861 - 1865
• Main Authors: TANG, NING, ZHANG, YA-PING, YING, WANG, YAO, XI-XIAN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.12.2013; Spandidos Publications UK Ltd
• Subjects: Animals; Anthracenes - pharmacology; Biotechnology; c-Jun N-terminal kinase; c-Jun protein; Cell culture; Cell Line; Collagen; Collagenase 3; Cytokines; Extracellular matrix; Fibrosis; Gene expression; Gene Expression Regulation, Enzymologic - drug effects; hepatic stellate cells; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - enzymology; IL-1β; Imidazoles - pharmacology; Interleukin-1beta - pharmacology; interleukin-1β; JNK Mitogen-Activated Protein Kinases - metabolism; JNK protein; Kinases; Liver; MAP kinase; MAP Kinase Signaling System - drug effects; MAPK; Matrix metalloproteinase; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 13 - metabolism; matrix metalloproteinase-13; Metalloproteinase; Models, Biological; p38; p38 Mitogen-Activated Protein Kinases - metabolism; Protein kinase; Proteins; Pyridines - pharmacology; Rats; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stellate cells; Studies; Time Factors; Transcription factors; Tumor necrosis factor-TNF; Up-Regulation - drug effects; Variance analysis; United States > US; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2013.1719

Matrix metalloproteinase-13 (MMP-13) is crucial in the cleavage and remodeling of the extracellular matrix (ECM), and its expression levels are decreased following the induction of liver fibrosis. The aim of the present study was to investigate the role of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in interleukin (IL)-1β-mediated MMP-13 gene expression in rat hepatic stellate cells (HSCs). In the present study, we demonstrated that IL-1β is capable of activating JNK and p38 in a time-dependent manner and the inhibition of the JNK pathway is able to increase MMP-13 mRNA expression; however, the inhibition of the p38 MAPK pathway is capable of inhibiting MMP-13 gene expression. These data demonstrate that IL-1β is able to promote MMP-13 mRNA expression in rat HSCs and the JNK and p38 MAPK pathways were involved in this process. In summary, IL-1β-induced MMP-13 mRNA expression is possibly mediated by cytoplasmic JNK and p38 MAPK pathways, and they play a distinct role in this process. Thus, the JNK and p38 MAPK pathway co-operatively mediate MMP-13 mRNA expression in rat HSCs.