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Syndecan-2 is a novel target of insulin-like growth factor binding protein-3 and is over-expressed in fibrosis

Ruiz, XD and Mlakar, LR and Yamaguchi, Y and Su, Y and Larregina, AT and Pilewski, JM and Feghali-Bostwick, CA (2012) Syndecan-2 is a novel target of insulin-like growth factor binding protein-3 and is over-expressed in fibrosis. PLoS ONE, 7 (8).

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Abstract

Extracellular matrix deposition and tissue scarring characterize the process of fibrosis. Transforming growth factor beta (TGFβ) and Insulin-like growth factor binding protein-3 (IGFBP-3) have been implicated in the pathogenesis of fibrosis in various tissues by inducing mesenchymal cell proliferation and extracellular matrix deposition. We identified Syndecan-2 (SDC2) as a gene induced by TGFβ in an IGFBP-3-dependent manner. TGFβ induction of SDC2 mRNA and protein required IGFBP-3. IGFBP-3 independently induced production of SDC2 in primary fibroblasts. Using an ex-vivo model of human skin in organ culture expressing IGFBP-3, we demonstrate that IGFBP-3 induces SDC2 ex vivo in human tissue. We also identified Mitogen-activated protein kinase-interacting kinase (Mknk2) as a gene induced by IGFBP-3. IGFBP-3 triggered Mknk2 phosphorylation resulting in its activation. Mknk2 independently induced SDC2 in human skin. Since IGFBP-3 is over-expressed in fibrotic tissues, we examined SDC2 levels in skin and lung tissues of patients with systemic sclerosis (SSc) and lung tissues of patients with idiopathic pulmonary fibrosis (IPF). SDC2 levels were increased in fibrotic dermal and lung tissues of patients with SSc and in lung tissues of patients with IPF. This is the first report describing elevated levels of SDC2 in fibrosis. Increased SDC2 expression is due, at least in part, to the activity of two pro-fibrotic factors, TGFβ and IGFBP-3. © 2012 Ruiz et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ruiz, XD
Mlakar, LR
Yamaguchi, Y
Su, Y
Larregina, ATadrianal@pitt.eduADRIANAL
Pilewski, JMpilewski@pitt.eduPILEWSKI
Feghali-Bostwick, CA
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorFuchs, SebastienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 10 August 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0043049
Schools and Programs: School of Medicine > Critical Care Medicine
School of Medicine > Dermatology
School of Medicine > Pathology
Refereed: Yes
Other ID: NLM PMC3416749
PubMed Central ID: PMC3416749
PubMed ID: 22900087
Date Deposited: 18 Oct 2012 16:48
Last Modified: 04 Feb 2019 15:56
URI: http://d-scholarship.pitt.edu/id/eprint/15883

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