Lumican, a small leucine‐rich proteoglycan

Nikitovic, Dragana; Katonis, Pavlos; Tsatsakis, Aristidis; Karamanos, Nikos K.; Tzanakakis, George N.

doi:10.1002/iub.131

Cited by 123 publications

(123 citation statements)

References 49 publications

(81 reference statements)

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“…Lessons from mice deficient in SLRPs indicate further functional overlap within this family (Ameye and Young 2002;Bi et al 2007;Schaefer et al 2002). Major functions of decorin (CS/DS PG), the prototype member of SLRPs, are summarized in Table 2 (for further details, we refer to more extensive reviews: Brandan et al 2008;Chakravarti 2002;Danielson et al 1999;Kao and Liu 2002;Nikitovic et al 2008;Roughley 2006;Schaefer and Iozzo 2008;Young et al 2006).…”

Section: Small Leucine-rich Pgsmentioning

confidence: 98%

Proteoglycans: from structural compounds to signaling molecules

2009

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Our knowledge of proteoglycan biology has significantly expanded over the past decade with the discovery of a host of new members of this multifunctional family leading to their present classification into three major categories: (1) small leucine-rich proteoglycans, 2) modular proteoglycans, and 3) cell-surface proteoglycans. In addition to being structural proteins, proteoglycans play a major role in signal transduction with regulatory functions in various cellular processes. Being mostly extracellular, they are upstream of many signaling cascades and are capable of affecting intracellular phosphorylation events and modulating distinct pathways, including those driven by bone morphogenetic protein/transforming growth factor superfamily members, receptor tyrosine kinases, the insulin-like growth factor-I receptor, and Toll-like receptors. Mechanistic insights into the molecular and cellular functions of proteoglycans have revealed both the sophistication of these regulatory proteins and the challenges that remain in uncovering the entirety of their biological functions. This review aims to summarize the multiple functions of proteoglycans with special emphasis on their intricate composition and the newly described signaling events in which these molecules play a key role.

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Section: Small Leucine-rich Pgsmentioning

confidence: 98%

Proteoglycans: from structural compounds to signaling molecules

2009

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“…Lumican has a protein core of ∼40 kDa, but is usually secreted as a higher molecular weight proteoglycan, with varying amounts keratan sulfate glycosaminoglycan (43,44). Lumican is vital for the correct formation of collagen fibrils and promotes cell adhesion and migration (40,(45)(46)(47).…”

Section: Significancementioning

confidence: 99%

TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

Pilling

Vakil

Cox

et al. 2015

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

109

103

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In healing wounds and fibrotic lesions, fibroblasts and monocyte-derived fibroblast-like cells called fibrocytes help to form scar tissue. Although fibrocytes promote collagen production by fibroblasts, little is known about signaling from fibroblasts to fibrocytes. In this report, we show that fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor necrosis factor-α secrete the small leucine-rich proteoglycan lumican, and that lumican, but not the related proteoglycan decorin, promotes human fibrocyte differentiation. Lumican competes with the serum fibrocyte differentiation inhibitor serum amyloid P, but dominates over the fibroblast-secreted fibrocyte inhibitor Slit2. Lumican acts directly on monocytes, and unlike other factors that affect fibrocyte differentiation, lumican has no detectable effect on macrophage differentiation or polarization. α2β1, αMβ2, and αXβ2 integrins are needed for lumican-induced fibrocyte differentiation. In lung tissue from pulmonary fibrosis patients with relatively normal lung function, lumican is present at low levels throughout the tissue, whereas patients with advanced disease have pronounced lumican expression in the fibrotic lesions. These data may explain why fibrocytes are increased in fibrotic tissues, suggest that the levels of lumican in tissues may have a significant effect on the decision of monocytes to differentiate into fibrocytes, and indicate that modulating lumican signaling may be useful as a therapeutic for fibrosis.

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“…LUM is a leucine-rich ECM glycoprotein that belongs to the small leucine-rich proteoglycan family of proteins. It interacts with collagen to maintain the integrity and function of connective tissues and has been implicated in various processes, such as cell migration, proliferation, wound healing and inflammation (Chakravarti 2003, Nikitovic et al 2008. There is increased transcription of LUM in glomeruli from human diabetic kidneys at different stages of nephropathy (Schaefer et al 2001).…”

Section: Structural Proteinsmentioning

confidence: 99%

2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue

Oliva

Barker

Rice

et al. 2013

Journal of Endocrinology

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Gestational diabetes mellitus (GDM) is a significant risk factor for the type 2 diabetes epidemic in many populations. Maternal adipose tissue plays a central role in the pathophysiology of GDM. Thus, the aim of this study was to determine the effect of GDM on the proteome of adipose tissue. Omental adipose tissue was obtained at the time of term Caesarean section from women with normal glucose tolerance (NGT) or GDM. 2D-difference gel electrophoresis (DIGE), followed by mass spectrometry, was used to identify protein spots (nZ6 patients per group). Western blotting was used for confirmation of six of the spot differences (nZ6 patients per group). We found 14 proteins that were differentially expressed between NGT and GDM adipose tissue (R1.4-fold, P!0.05). GDM was associated with an up-regulation of four proteins: collagen alpha-2(VI) chain (CO6A2 (COL6A2)), fibrinogen beta chain (FIBB (FGB)), lumican (LUM) and S100A9. On the other hand, a total of ten proteins were found to be down-regulated in adipose tissue from GDM women. These were alpha-1-antitrypsin (AIAT (SERPINA1)), annexin A5 (ANXA5), fatty acid-binding protein, adipocyte (FABP4), glutathione S-transferase P (GSTP (GSTP1)), heat-shock protein beta-1 (HSP27 (HSPB1)), lactate dehydrogenase B chain (LDHB), perilipin-1 (PLIN1), peroxiredoxin-6 (PRX6 (PRDX6)), selenium-binding protein 1 (SBP1) and vinculin (VINC (VCL)). In conclusion, proteomic analysis of omental fat reveals differential expression of several proteins in GDM patients and NGT pregnant women. This study revealed differences in expression of proteins that are involved in inflammation, lipid and glucose metabolism and oxidative stress and added further evidence to support the role of visceral adiposity in the pathogenesis of GDM.

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Lumican, a small leucine‐rich proteoglycan

Cited by 123 publications

References 49 publications

Proteoglycans: from structural compounds to signaling molecules

Proteoglycans: from structural compounds to signaling molecules

TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue

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