Collagen fibril organization in the pregnant endometrium of decorin‐deficient mice

Sanches, Juliane Cristina Trevisan; Jones, Carolyn J.P.; Aplin, John D.; Iozzo, Renato V.; Zorn, Telma Maria Tenório; Oliveira, Sérgio Ferreira de

doi:10.1111/j.1469-7580.2009.01170.x

Cited by 23 publications

(26 citation statements)

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“…Undoubtedly, SLRPs are structural components especially important during development and the maturation of various tissues enriched in mesenchyme. Utilization of animal models including the mouse [7,40,88–101] and zebrafish [102], or cellular systems with finite SLRP deficiencies [83,103–105], has revealed fundamental roles for SLRPs in embryonic life and disease progression. The past decade has further witnessed many members of the SLRP gene family emerging as signaling molecules.…”

Section: Discussionmentioning

confidence: 99%

Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine‐rich proteoglycans

2010

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The small leucine‐rich proteoglycans (SLRPs) are involved in many aspects of mammalian biology, both in health and disease. They are now being recognized as key signaling molecules with an expanding repertoire of molecular interactions affecting not only growth factors, but also various receptors involved in controlling cell growth, morphogenesis and immunity. The complexity of SLRP signaling and the multitude of affected signaling pathways can be reconciled with a hierarchical affinity‐based interaction of various SLRPs in a cell‐ and tissue‐specific context. Here, we review this interacting network, describe new relationships of the SLRPs with tyrosine kinase and Toll‐like receptors and critically assess their roles in cancer and innate immunity.

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Section: Discussionmentioning

confidence: 99%

Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine‐rich proteoglycans

2010

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“…Biglycan is expressed in the pregnant mouse uterus (San Martin et al 2003, San Martin & Zorn 2003), while both biglycan and decorin are decreased in the human myometrium during labor (Hjelm et al 2002). In decorin homozygous null mutant mice, the decidualized stroma of the uterus shows abnormal collagen architecture with large diameters and irregular contours (Sanches et al 2010). Furthermore, these SLRPs are the most abundant proteoglycans expressed in human fetal membranes (Gogiel & Jaworski 2000, Meinert et al 2001, Gogiel et al 2003, Valiyaveettil et al 2004).…”

Section: Introductionmentioning

confidence: 99%

A mouse model of spontaneous preterm birth based on the genetic ablation of biglycan and decorin

Calmus¹,

Macksoud²,

Tucker³

et al. 2011

Reproduction

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Preterm premature rupture of membranes is responsible for one third of preterm births. Ehlers-Danlos syndrome (EDS) is associated with preterm premature rupture of membranes in humans. Notably, an EDS variant is caused by a genetic mutation resulting in abnormal secretion of biglycan and decorin, two small leucine-rich proteoglycans highly expressed in reproductive tissues. Because biglycan/decorin null mutant (Bgn−/−Dcn−/−) mice demonstrate phenotypic changes similar to EDS, we utilized this model to test whether either or both biglycan and decorin play a role in the attainment of successful term gestation. Wild-type, biglycan null mutant, decorin null mutant and biglycan/decorin null mutant pregnancies were assessed for length of gestation, pup and placenta weight and litter size. Quantitative real-time polymerase chain reaction was performed to measure biglycan and decorin gene expression and immunohistochemistry was performed to assess protein expression in placenta and fetal membranes at embryonic day E12, E15 and E18. Bgn−/−Dcn−/− dams displayed preterm birth, whereas the possession of at least two biglycan or decorin wild-type alleles was protective of preterm birth. Bgn−/−Dcn−/− pups were decreased at postnatal day P1 but not at E18. Biglycan and decorin were upregulated in the placenta in each other’s absence and were developmentally regulated in fetal membranes, suggesting that these two proteoglycans demonstrate genetic complementation and contribute to gestational success in a dose dependent manner. Thus, the biglycan/decorin null mutant mouse is a model of genetically induced preterm birth and perinatal loss. This model presents novel targets for preventive or therapeutic manipulation of preterm birth.

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“…Genetic and biochemical studies have revealed that many of the matrix components are indeed signaling molecules that can affect the behavior of cells during development and disease progression (2). Decorin, a prototype member of the small leucine-rich proteoglycans (SLRPs) 3 (3)(4)(5)(6)(7)(8), is involved in a multitude of biological processes including collagen fibrillogenesis (9 -12), modulation of various growth factors and receptors (13)(14)(15)(16)(17)(18)(19)(20)(21)(22), renal diseases (23)(24)(25), angiogenesis (26,27), wound healing (28), myocardial infarction (29), lung and tendon mechanics (30 -32), infectious diseases (33,34), bone and tooth development (35,36), connective tissue development (37)(38)(39)(40)(41), and bone marrow stromal cell biology (42).…”

mentioning

confidence: 99%

Decorin Antagonizes Met Receptor Activity and Down-regulates β-Catenin and Myc Levels

Buraschi

Pal

Tyler-Rubinstein

et al. 2010

Journal of Biological Chemistry

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121

153

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A theme emerging during the past few years is that members of the small leucine-rich proteoglycan gene family affect cell growth by interacting with multiple receptor tyrosine kinases (RTKs), mostly by a physical down-regulation of the receptors, thereby depriving tumor cells of pro-survival signals. Decorin binds and down-regulates several RTKs, including Met, the receptor for hepatocyte growth factor. Here we demonstrate that decorin blocks several biological activities mediated by the Met signaling axis, including cell scatter, evasion, and migration. These effects were mediated by a profound down-regulation of noncanonical ␤-catenin levels. In addition, Myc, a downstream target of ␤-catenin, was markedly down-regulated by decorin, whereas phosphorylation of Myc at threonine 58 was markedly induced. The latter is known to destabilize Myc and target it for proteasomal degradation. We also discovered that systemic delivery of decorin using three distinct tumor xenograft models caused down-regulation of Met and a concurrent suppression of ␤-catenin and Myc levels. We found that decorin protein core labeled with the near infrared dye IR800 specifically targeted the tumor cells expressing Met. Even 68-h post-injection, decorin was found to reside within the tumor xenografts with little or no binding to other tissues. Collectively, our results indicate a role for a secreted proteoglycan in suppressing the expression of key oncogenic factors required for tumor progression.Biological activities are triggered, modulated, and maintained mostly by the complex interplay among extracellular matrix molecules, multifunctional growth factors, and their surface receptors (1). Genetic and biochemical studies have revealed that many of the matrix components are indeed signaling molecules that can affect the behavior of cells during development and disease progression (2). Decorin, a prototype member of the small leucine-rich proteoglycans (SLRPs) 3 (3-8), is involved in a multitude of biological processes including collagen fibrillogenesis (9 -12), modulation of various growth factors and receptors (13-22), renal diseases (23-25), angiogenesis (26, 27), wound healing (28), myocardial infarction (29), lung and tendon mechanics (30 -32), infectious diseases (33, 34), bone and tooth development (35, 36), connective tissue development (37-41), and bone marrow stromal cell biology (42).The involvement of decorin in cancer progression has been demonstrated in mutant mice. Although the decorin-null mice do not spontaneously develop malignant neoplasms, mice carrying a targeted deletion of both decorin and the tumor suppressor p53 succumb within 3-4 months to aggressive lymphomas at a rate faster than p53-null mice alone (43), suggesting that decorin is permissive for tumorigenesis. In accordance with this study, ϳ30% of decorin-null animals, which were backcrossed into a different genetic background, displayed spontaneous occurrence of intestinal tumors, and both the tumor burden and frequency were enhanced by subjecting the mutant mi...

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Collagen fibril organization in the pregnant endometrium of decorin‐deficient mice

Cited by 23 publications

References 56 publications

Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine‐rich proteoglycans

Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine‐rich proteoglycans

A mouse model of spontaneous preterm birth based on the genetic ablation of biglycan and decorin

Decorin Antagonizes Met Receptor Activity and Down-regulates β-Catenin and Myc Levels

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