Abstract：
:Glomerular mesangial cells (MCs) are central to the pathogenesis of progressive glomeruli-associated renal diseases. However, molecular mechanisms underlying changes in MC functions still remain poorly understood. Here, we show that in MCs, the urokinase-type plasminogen activator (uPA) induces, via its specific receptor (uPAR, CD87), upregulated expression of the complement anaphylatoxin C5a receptor (C5aR, CD88), and modulates C5a-dependent functional responses. This effect is mediated via the interaction of the uPA-specific receptor (uPAR, CD87) and gp130, a signal transducing subunit of the receptor complexes for the IL-6 cytokine family. The Janus kinase Tyk2 and the transcription factor Stat3 serve as downstream components in the signaling cascade resulting in upregulation of C5aR expression. In vivo, expression of C5aR and uPAR was increased in the mesangium of wild-type mice in a lipopolysaccharide (LPS)-induced model of inflammation, whereas in uPAR(-/-) animals C5aR expression remained unchanged. This is the first demonstration in vitro and in vivo that uPA acts in MCs as a modulator of immune responses via control of immune-competent receptors. The data suggest a novel role for uPA/uPAR in glomeruli-associated renal failure via a signaling cross-talk between the fibrinolytic and immune systems.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Shushakova N,Tkachuk N,Dangers M,Tkachuk S,Park JK,Hashimoto K,Haller H,Dumler Idoi
10.1242/jcs.02409keywords:
subject
Has Abstractpub_date
2005-06-15 00:00:00pages
2743-53issue
Pt 12eissn
0021-9533issn
1477-9137pii
118/12/2743journal_volume
118pub_type
杂志文章abstract：:The cornified cell envelope (CE), a structure formed in the outermost layers of stratified squamous epithelia, provides a physical barrier against environmental insults. It is composed of several structural proteins, which are irreversibly crosslinked by calcium-activated transglutaminases. The small proline rich prot...
journal_title：Journal of cell science
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abstract：:Wound healing crucially relies on the mechanical activity of fibroblasts responding to TGFβ1 and to forces transmitted across focal adhesions. Integrin-linked kinase (ILK) is a central adapter recruited to integrin β1 tails in focal adhesions mediating the communication between cells and extracellular matrix. Here, we...
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journal_title：Journal of cell science
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更新日期：2002-01-01 00:00:00
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更新日期：2005-10-15 00:00:00
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doi：
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