title: Overexpression of biglycan in the heart of transgenic mice: an antibody microarray study.
abstract: Biglycan, a small leucine rich proteoglycan, is expressed in almost every tissue of the body, mainly in the extracellular matrix of connective tissues. Although there is an increasing amount of data on the biological role of biglycan protein, its function is still poorly understood. We aimed to gather more information about the biological function of biglycan protein in the cardiac tissues, and its role in signal transduction. Therefore, we generated transgenic mice overexpressing the human biglycan protein and analyzed the cardiac protein profile of transgenic offsprings using quantitative real-time (QRT)-PCR and proteomics. QRT-PCR results showed that most members of extracellular matrix were downregulated whereas cadherins, TGF-beta1, and TGF-beta2 were upregulated. Antibody microarrayer experiment revealed that pyk2, RAF-1, Mcl-1, syntrophin, calmodulin, isoforms of NOS protein family (eNOS, nNOS, and iNOS), and synaptotagmin proteins were unambiguously upregulated in the heart of biglycan transgenic mice. In this study we show that biglycan directly or indirectly activates proteins involved in cardiac remodeling (TGF-beta, pyk2), signal transduction (RAF-1, Mcl-1, syntrophin, calmodulin, nNOS p38MAPK and MAP kinases), cardioprotection (NOS family, TGF-beta) and Ca++ signaling (connexin, calmodulin, synaptotagmin). On the basis of the results presented here, we conclude that biglycan is a multifunctional extracellular protein that has a pivotal role in pathological remodeling of cardiac tissue and mediates cardioprotection.
authors.affiliation: Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, H-6701 Szeged, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Bereczki
authors.forename: Szilvia
authors.initials: S
authors.lastname: Gonda
authors.forename: Tamas
authors.initials: T
authors.lastname: Csont
authors.forename: Eva
authors.initials: E
authors.lastname: Korpos
authors.forename: Agnes
authors.initials: A
authors.lastname: Zvara
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
authors.forename: Miklós
authors.initials: M
authors.lastname: Santha
mesh_terms: D000818:Animals; D000906:Antibodies; D000917:Antibody Formation; D001011:Aorta / Q000502:physiology; D058578:Biglycan; D002316:Cardiotonic Agents; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000276:immunology; D006321:Heart / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000502:physiology; D040081:Protein Array Analysis; D011509:Proteoglycans / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000906:Antibodies; C546884:BGN protein, human; C546885:Bgn protein, mouse; D058578:Biglycan; D002316:Cardiotonic Agents; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans