Thrombin Promotes Matrix Metalloproteinase-13 Expression through the PKCδc-SrcEGFRPI3KAktAP-1 Signaling Pathway in Human Chondrocytes
Joint Authors
Huang, Chun-Yin
Tang, Chih-Hsin
Hsu, Horng-Chaung
Cheng, Shi-Yann
Chen, Hsin-Shui
Lin, Hsiu-Jung
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-12-09
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Thrombin is a key mediator of fibrin deposition, angiogenesis, and proinflammatory processes.
Abnormalities in these processes are primary features of rheumatoid arthritis and osteoarthritis.
Matrix metalloproteinase-13 (MMP-13) may contribute to the breakdown of articular cartilage during arthritis.
However, the role of thrombin in MMP-13 production in chondrocytes is unknown.
In this study, we investigated the intracellular signaling pathways involved in thrombin-induced MMP-13 expression in human chondrocytes.
We found that stimulation with thrombin led to increased secretion of MMP-13 in cultured human chondrocytes.
Further, this thrombin-induced MMP-13 production was reduced after transfection with siRNAs against protease activated receptors 1 and 3 (PAR1 and PAR3), but not with PAR4 siRNA.
Treatment with specific inhibitors for PKCδ, c-Src, EGFR, PI3K, Akt, or AP-1 or with the corresponding siRNAs against these signaling proteins also abolished the thrombin-mediated increase in MMP-13 production in chondrocytes.
Our results provide evidence that thrombin acts through the PAR1/PAR3 receptors and activates PKCδ and c-Src, resulting in EGFR transactivation and activation of PI3K, Akt, and finally AP-1 on the MMP-13 promoter, thereby contributing to cartilage destruction during arthritis.
American Psychological Association (APA)
Huang, Chun-Yin& Lin, Hsiu-Jung& Chen, Hsin-Shui& Cheng, Shi-Yann& Hsu, Horng-Chaung& Tang, Chih-Hsin. 2013. Thrombin Promotes Matrix Metalloproteinase-13 Expression through the PKCδc-SrcEGFRPI3KAktAP-1 Signaling Pathway in Human Chondrocytes. Mediators of Inflammation،Vol. 2013, no. 2013, pp.1-12.
https://search.emarefa.net/detail/BIM-463702
Modern Language Association (MLA)
Huang, Chun-Yin…[et al.]. Thrombin Promotes Matrix Metalloproteinase-13 Expression through the PKCδc-SrcEGFRPI3KAktAP-1 Signaling Pathway in Human Chondrocytes. Mediators of Inflammation No. 2013 (2013), pp.1-12.
https://search.emarefa.net/detail/BIM-463702
American Medical Association (AMA)
Huang, Chun-Yin& Lin, Hsiu-Jung& Chen, Hsin-Shui& Cheng, Shi-Yann& Hsu, Horng-Chaung& Tang, Chih-Hsin. Thrombin Promotes Matrix Metalloproteinase-13 Expression through the PKCδc-SrcEGFRPI3KAktAP-1 Signaling Pathway in Human Chondrocytes. Mediators of Inflammation. 2013. Vol. 2013, no. 2013, pp.1-12.
https://search.emarefa.net/detail/BIM-463702
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-463702