The Murine Biglycan: Complete cDNA Cloning, Genomic Organization, Promoter Function, and Expression

Wegrowski, Yanusz; Pillarisetti, Jhuma; Danielson, Keith G.; Suzuki, Shintaro; Iozzo, Renato V.

doi:10.1006/geno.1995.0002

Cited by 58 publications

(41 citation statements)

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“…By immunohistochemistry and real-time RT-PCR, BGN was detected in mouse dermis as has been shown before. 45 However, the expression of BGN was affected neither during intrinsic aging nor by UVB. These data suggest that UVB-induced loss of HA and downregulation of HAS are specific responses and not part of a general down-regulation of polysaccharides and proteoglycans.…”

Section: Discussionmentioning

confidence: 97%

Chronic Ultraviolet B Irradiation Causes Loss of Hyaluronic Acid from Mouse Dermis Because of Down-Regulation of Hyaluronic Acid Synthases

Dai

Freudenberger

Zipper

et al. 2007

The American Journal of Pathology

142

116

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Remodeling of the dermal extracellular matrix occurs during photoaging. Here, the effect of repetitive UVB irradiation on dermal hyaluronic acid (HA) was examined. C57/BL6 mice were chronically (182 days) irradiated with UVB, and consecutive skin biopsies were collected during the irradiation period and afterward (300 and 400 days of age). UVB caused marked loss of HA from the papillary dermis and down-regulation of HA synthase 1 (HAS1), HAS2, and HAS3 mRNA expression. In contrast, hyaluronidases (HYAL) 1, HYAL2, and HA receptor CD44 were unchanged. Furthermore, transforming growth factor ␤-1 (TGF-␤1) and TGF-␤1-receptor II expression were decreased in UVB-irradiated biopsies, and TGF-␤1 strongly induced HAS1 and HAS2 expression in cultured dermal fibroblasts. Therefore, TGF-␤1 might be one factor involved in UVB-induced down-regulation of HAS enzymes. In addition, total cell number and the percentage of proliferating fibroblasts in the papillary dermis of UVB-irradiated mice were decreased. Down-regulation of HAS2 by lentiviral overexpression of short hairpin RNA in vitro caused inhibition of HA synthesis, DNA synthesis, and migration of dermal fibroblasts. In conclusion, chronic UVB irradiation induces loss of HA from the dermis, thereby contributing to the quiescent phenotype of dermal fibroblasts. 1 Photoaging is the most common form of skin damage caused by chronic, repetitive sun exposure.2 The long-term exposure to solar UV irradiation induces damage to the dermal connective tissue and the extracellular matrix (ECM), which in turn leads to the aged appearance of photodamaged skin. Hallmark of this UV-induced ECM remodeling is the degradation of collagen and elastin through the UVB-induced activation of matrix metalloproteinases and decreased de novo synthesis of collagen. The mechanisms of UVB-induced matrix metalloproteinase activation 3 and inhibition of collagen synthesis have been studied in detail.2 In contrast the effect of UVB on hyaluronic acid (HA), another key component of the dermal ECM, is much less understood, and the underlying mechanisms are primarily unknown. HA is a linear polymer composed of repeating disaccharides (D-glucuronic acid-␤-1,3-N-acetylglucosamine-␤-1,4-) and assembled from the respective activated nucleotide sugars (UDPglucuronic acid, UDP-N-acetylglucosamine) at the inner plasma membrane by HA synthases (HAS). Three different HAS isoforms are known that reside in the plasma membrane and extrude the growing HA polymer into the extracellular space.4 HAS1 and HAS2 produce high molecular mass HA (2 to 4 ϫ 10 6 Da), whereas HAS3 synthesizes smaller HA (0.4 to 2.5 ϫ 10 5 Da). 5 The variation of the MW is the only modification of HA because O-or N-sulfations do not occur. HA is an agonist of CD44 and RHAMM (receptor of HA-mediated motility), which enables HA to initiate specific signaling events.6 This receptor signaling and the formation of pericellular HA coats supports proliferation and migration of a variety of cell types including skin fibroblasts. 7 In addition, antiapoptoti...

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Section: Discussionmentioning

confidence: 97%

Chronic Ultraviolet B Irradiation Causes Loss of Hyaluronic Acid from Mouse Dermis Because of Down-Regulation of Hyaluronic Acid Synthases

Dai

Freudenberger

Zipper

et al. 2007

The American Journal of Pathology

142

116

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“…The enhanced Wnt-induced signaling could be completely inhibited by the extracellular Wnt inhibitor Dkk1, confirming biglycan's extracellular role in mediating Wnt function. Although we used bone as a model system in this study, our findings may have important implications for two reasons, given biglycan's wide tissue distribution (15,16,32). First, biglycan is likely to play a physiological role in the control of Wnt/β-catenin signaling.…”

Section: Discussionmentioning

confidence: 99%

Modulation of canonical Wnt signaling by the extracellular matrix component biglycan

Berendsen

Fisher

Kilts

et al. 2011

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

135

136

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Although extracellular control of canonical Wnt signaling is crucial for tissue homeostasis, the role of the extracellular microenvironment in modulating this signaling pathway is largely unknown. In the present study, we show that a member of the small leucine-rich proteoglycan family, biglycan, enhances canonical Wnt signaling by mediating Wnt function via its core protein. Immunoprecipitation analysis revealed that biglycan interacts with both the canonical Wnt ligand Wnt3a and the Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6), possibly via the formation of a trimeric complex. Biglycan-deficient cells treated with exogenous Wnt3a had less Wnt3a retained in cell layers compared with WT cells. Furthermore, the Wnt-induced levels of LRP6 phosphorylation and expression of several Wnt target genes were blunted in biglycan-deficient cells. Both recombinant biglycan proteoglycan and biglycan core protein increased Wnt-induced β-catenin/T cell-specific factor–mediated transcriptional activity, and this activity was completely inhibited by Dickkopf 1. Interestingly, recombinant biglycan was able to rescue impaired Wnt signaling caused by a previously described missense mutation in the extracellular domain of human LRP6 (R611C). Furthermore, biglycan's modulation of canonical Wnt signaling affected the functional activities of osteoprogenitor cells, including the RUNX2-mediated transcriptional activity and calcium deposition. Use of a transplant system and a fracture healing model revealed that expression of Wnt-induced secreted protein 1 was decreased in bone formed by biglycan-deficient cells, further suggesting reduced Wnt signaling in vivo. We propose that biglycan may serve as a reservoir for Wnt in the pericellular space and modulate Wnt availability for activation of the canonical Wnt pathway.

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“…Plasmid Construction-Deletion constructs cloned upstream of the CAT reporter gene within the pUC or pBluescript (pBS) vector (Stratagene) were generated as described before (28). The 2.5-kb 5Ј-flanking region linked to exon 1 (86 bp) was subcloned into the pBS vector and then subcloned into the respective sites in the pUC-CAT vector.…”

Section: Materials and Cell Cultures-radionucleotidesmentioning

confidence: 99%

“…Transient Cell Transfection and CAT Assays-Transient transfections of cell types were performed by the calcium phosphate procedure essentially as described before (28,29). Briefly, subconfluent cells in 75-cm 2 flasks were trypsinized, washed, and co-transfected in suspension with 20 -40 g of perlecan promoter-CAT constructs and 10 g of pSV-␤-galactosidase plasmid to provide an internal standard for normalization of the values.…”

Section: Materials and Cell Cultures-radionucleotidesmentioning

confidence: 99%

Structural and Functional Characterization of the Human Perlecan Gene Promoter

Iozzo

Pillarisetti²,

Sharma³

et al. 1997

Journal of Biological Chemistry

Self Cite

100

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Perlecan, a modular heparan sulfate proteoglycan of basement membranes and cell surfaces, plays a crucial role in regulating the assembly of extracellular matrices and the binding of nutrients and growth factors to target cells. To achieve a molecular understanding of perlecan gene regulation, we isolated the 5-flanking region and investigated its functional promoter activity and its response to cytokines. Transient cell transfection assays, using plasmid constructs harboring the perlecan promoter linked to the chloramphenicol acetyltransferase reporter gene, demonstrated that the largest ϳ2.5-kilobase construct contained maximal promoter activity. This promoter region was functionally active in a variety of cells of diverse histogenetic origin, thus corroborating the widespread expression of this gene product. Stepwise 5 deletion analyses demonstrated that the ؊461-base pair (bp) proximal promoter retained ϳ90% of the total activity, and internal deletions confirmed that the most proximal sequence was essential for proper promoter activity. Nanomolar amounts of transforming growth factor-␤ induced 2-3-fold perlecan mRNA and protein core levels in normal human skin fibroblasts, and this induction was transcriptionally regulated; in contrast, tumor necrosis factor-␣ had no effect and was incapable of counteracting the effects of TGF-␤. Using additional 5 deletions and DNase footprinting analyses, we mapped the TGF-␤ responsive region to a sequence of 177 bp contained between ؊461 and ؊285. This region harbored a 14-bp element similar to a TGF-␤-responsive element present in the promoters of collagen ␣1(I), ␣2(I), elastin, and growth hormone. Electrophoretic mobility shift assays and mutational analyses demonstrated that the perlecan TGF-␤-responsive element bound specifically to TGF-␤-inducible nuclear proteins with high affinity for NF-1 member(s) of transcription factors.

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The Murine Biglycan: Complete cDNA Cloning, Genomic Organization, Promoter Function, and Expression

Cited by 58 publications

References 0 publications

Chronic Ultraviolet B Irradiation Causes Loss of Hyaluronic Acid from Mouse Dermis Because of Down-Regulation of Hyaluronic Acid Synthases

Chronic Ultraviolet B Irradiation Causes Loss of Hyaluronic Acid from Mouse Dermis Because of Down-Regulation of Hyaluronic Acid Synthases

Modulation of canonical Wnt signaling by the extracellular matrix component biglycan

Structural and Functional Characterization of the Human Perlecan Gene Promoter

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