Expression and Localization of Lumican in the Ischemic and Reperfused Rat Heart.

Baba, Hideyuki; Ishiwata, Toshiyuki; Takashi, En; Xu, Guang; Asano, Gorō

doi:10.1253/jcj.65.445

Cited by 51 publications

(37 citation statements)

References 18 publications

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“…For example, Lum is a member of leucine-rich proteoglycan family that is thought to regulate the assembly and diameter of collagen fibers (16), and both Lum and Col1a1 are associated with the pathology of fibrosis in heart (17,18). We show that Col1a1 has multivariant HF-, sex-, and age-dependent components.…”

Section: Discussionmentioning

confidence: 76%

Sex- and age-dependent human transcriptome variability: Implications for chronic heart failure

Boheler

Volkova

Morrell

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Heart failure (HF) is the end result of progressive and diverse biological adaptations within the diseased myocardium. We used cDNA microarrays and quantitative PCR to examine the transcriptomes of 38 left ventricles from failing and nonfailing human myocardium. After identification of a pool of putative HF-responsive candidate genes by microarrays on seven nonfailing and eight failing hearts, we used quantitative PCR and a general linear statistical model in a larger sample set (n ‫؍‬ 34) to validate and examine the role of contributing biological variables (age and sex). We find that most HF-candidate genes (transcription factors, Cebpb, Npat; signaling molecules, Map2k3, Map4k5; extracellular matrix proteins, Lum, Cola1; and metabolic enzymes, Mars) demonstrated significant changes in gene expression; however, the majority of differences among samples depended on variables such as sex and age, and not on HF alone. Some HF-responsive gene products also demonstrated highly significant changes in expression as a function of age and͞or sex, but independent of HF (Ngp1, Cd163, and Npat). These results emphasize the need to account for biological variables (HF, sex and age interactions) to elucidate genomic correlates that trigger molecular pathways responsible for the progression of HF syndromes.

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Section: Discussionmentioning

confidence: 76%

Sex- and age-dependent human transcriptome variability: Implications for chronic heart failure

Boheler

Volkova

Morrell

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Although information about the function of lumican in normal and diseased hearts is scarce, a few studies by our group 120, 121, 220 and others 124,125 have shown that lumican levels are altered in the remodeling heart. Importantly, protein levels of lumican correlated positively with lung weight during pressure overload-induced remodeling, suggesting an association between lumican and development of congestive heart failure.…”

Section: The Multiple Roles Of Syndecan-4 In Cardiac Remodelingmentioning

confidence: 98%

“…122 Mice deficient in lumican develop opacities of the cornea and fragile skin, due to abnormal fibril assembly and altered interfibrillar spacing. 123 Interestingly, recent reports have shown that lumican levels are altered in the diseased heart, 120,121,124,125 indicating that it may regulate ECM structure also during heart failure progression. In this thesis, we studied lumican in cardiac fibroblasts and failing hearts.…”

Section: Small Leucine-rich Proteoglycansmentioning

confidence: 99%

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

et al. 2013

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Sustained pressure overload induces heart failure, the main cause of mortality in the Western world. Increased understanding of the underlying molecular mechanisms is essential to improve heart failure treatment. Despite important functions in other tissues, cardiac proteoglycans have received little attention. Syndecan‐4, a transmembrane heparan sulfate proteoglycan, is essential for pathological remodeling, and we here investigated its expression and shedding during heart failure. Pressure overload induced by aortic banding for 24 h and 1 week in mice increased syndecan‐4 mRNA, which correlated with mRNA of inflammatory cytokines. In cardiac myocytes and fibroblasts, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide through the toll‐like receptor‐4, induced syndecan‐4 mRNA. Bioinformatical and mutational analyses in HEK293 cells identified a functional site for the proinflammatory nuclear factor‐κB transcription factor in the syndecan‐4 promoter, and nuclear factor‐κB regulated syndecan‐4 mRNA in cardiac cells. Interestingly, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide induced nuclear factor‐κB‐dependent shedding of the syndecan‐4 ectodomain from cardiac cells. Overexpression of syndecan‐4 with mutated enzyme‐interacting domains suggested enzyme‐dependent heparan sulfate chains to regulate shedding. In cardiac fibroblasts, lipopolysaccharide reduced focal adhesion assembly, shown by immunohistochemistry, suggesting that inflammation‐induced shedding affects function. After aortic banding, a time‐dependent cardiac recruitment of T lymphocytes was observed by measuring CD3, CD4 and CD8 mRNA, which was reduced in syndecan‐4 knockout hearts. Finally, syndecan‐4 mRNA and shedding were upregulated in failing human hearts. Conclusively, our data suggest that syndecan‐4 plays an important role in the immune response of the heart to increased pressure, influencing cardiac remodeling and failure progression.

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“…However, increased lumican expression in rat heart after ischemia/reperfusion consists of both the proteoglycan and the glycoprotein, which are differentially expressed during different phases of wound healing. 160 Indeed, alterations in glycosylation of decorin and lumican core protein in response to pressure overload might be important in cardiac remodeling, with a potential important role for CS/DS GAG chain-synthesizing enzymes. 161 Interestingly, both lumican and decorin can be cleaved by MMP-1, suggesting that proteolytic processing is very precisely regulated and crucial for proteoglycan-mediated spatiotemporal functions.…”

Section: Class II Slrps: Lumicanmentioning

confidence: 99%

Myocardial Extracellular Matrix

Rienks

Papageorgiou

Frangogiannis

et al. 2014

Circulation Research

307

170

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Abstract:The cardiac extracellular matrix (ECM) is a complex architectural network consisting of structural and nonstructural proteins, creating strength and plasticity. The nonstructural compartment of the ECM houses a variety of proteins, which are vital for ECM plasticity, and can be divided into 3 major groups: glycoproteins, proteoglycans, and glycosaminoglycans. The common denominator for these groups is glycosylation, which refers to the decoration of proteins or lipids with sugars. This review will discuss the fundamental role of the matrix in cardiac development, homeostasis, and remodeling, from a glycobiology point of view. Glycoproteins (eg, thrombospondins, secreted protein acidic and rich in cysteine, tenascins), proteoglycans (eg, versican, syndecans, biglycan), and glycosaminoglycans (eg, hyaluronan, heparan sulfate) are upregulated on cardiac injury and regulate key processes in the remodeling myocardium such as inflammation, fibrosis, and angiogenesis. Albeit some parallels can be made regarding the processes these proteins are involved in, their specific functions are extremely diverse. In fact, under varying conditions, individual proteins can even have opposing functions, making spatiotemporal contribution of these proteins in the rearrangement of multifaceted ECM very hard to grasp. Alterations of protein characteristics by the addition of sugars may explain the immense, yet tightly regulated, variability of the remodeling cardiac matrix. Understanding the role of glycosylation in altering the ultimate function of glycoproteins, proteoglycans, and glycosaminoglycans in the myocardium may lead to the development of new biochemical structures or compounds with great therapeutic potential for patients with heart disease. (Circ Res. 2014;114:872-888.)

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Expression and Localization of Lumican in the Ischemic and Reperfused Rat Heart.

Cited by 51 publications

References 18 publications

Sex- and age-dependent human transcriptome variability: Implications for chronic heart failure

Sex- and age-dependent human transcriptome variability: Implications for chronic heart failure

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

Myocardial Extracellular Matrix

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