Small proline-rich protein 1A is a gp130 pathway- and stress-inducible cardioprotective protein.

Details

Serval ID
serval:BIB_FA8FEA57B4B2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Small proline-rich protein 1A is a gp130 pathway- and stress-inducible cardioprotective protein.
Journal
EMBO Journal
Author(s)
Pradervand S., Yasukawa H., Muller O.G., Kjekshus H., Nakamura T., St Amand T.R., Yajima T., Matsumura K., Duplain H., Iwatate M., Woodard S., Pedrazzini T., Ross J., Firsov D., Rossier B.C., Hoshijima M., Chien K.R.
ISSN
0261-4189 (Print)
ISSN-L
0261-4189
Publication state
Published
Issued date
2004
Volume
23
Number
22
Pages
4517-4525
Language
english
Abstract
The interleukin-6 cytokines, acting via gp130 receptor pathways, play a pivotal role in the reduction of cardiac injury induced by mechanical stress or ischemia and in promoting subsequent adaptive remodeling of the heart. We have now identified the small proline-rich repeat proteins (SPRR) 1A and 2A as downstream targets of gp130 signaling that are strongly induced in cardiomyocytes responding to biomechanical/ischemic stress. Upregulation of SPRR1A and 2A was markedly reduced in the gp130 cardiomyocyte-restricted knockout mice. In cardiomyocytes, MEK1/2 inhibitors prevented SPRR1A upregulation by gp130 cytokines. Furthermore, binding of NF-IL6 (C/EBPbeta) and c-Jun to the SPRR1A promoter was observed after CT-1 stimulation. Histological analysis revealed that SPRR1A induction after mechanical stress of pressure overload was restricted to myocytes surrounding piecemeal necrotic lesions. A similar expression pattern was found in postinfarcted rat hearts. Both in vitro and in vivo ectopic overexpression of SPRR1A protected cardiomyocytes against ischemic injury. Thus, this study identifies SPRR1A as a novel stress-inducible downstream mediator of gp130 cytokines in cardiomyocytes and documents its cardioprotective effect against ischemic stress.
Keywords
Adenoviridae/genetics, Animals, Animals, Newborn, Antigens, CD/metabolism, Blotting, Western, Cardiotonic Agents/metabolism, Cell Survival, Cornified Envelope Proline-Rich Proteins, Crosses, Genetic, Cytokine Receptor gp130, Fluorescent Dyes, Gene Expression Regulation, Hydrazines, Interleukin-6/genetics, Interleukin-6/secretion, Membrane Glycoproteins/metabolism, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Models, Biological, Myocardial Reperfusion Injury, Myocardium/cytology, Myocardium/metabolism, Myocytes, Cardiac/cytology, Myocytes, Cardiac/metabolism, Oligonucleotide Array Sequence Analysis, Promoter Regions, Genetic, Proteins/metabolism, Signal Transduction
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 13:32
Last modification date
20/08/2019 17:26
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