Abstract
The hallmark of failing renal transplants is tubular atrophy and interstitial fibrosis. The cytokine connective tissue growth factor (CTGF or CCN2) plays an important role in epithelial-mesenchymal transition (EMT) of tubular epithelial cells (TECs). A unique domain within CTGF (IRTPKISKPIKFELSG) which binds to its potential receptor integrin alpha v beta3 has been identified. This study was carried out to further characterize a synthetic hexadeca-peptide (P2) homologous to this domain and to determine its effect on CTGF-mediated solid phase cell adhesion, EMT induction and fibrogenesis in rat renal NRK-52E cells. Results showed that both P2 and recombinant CTGF bound to NRK-52E cells. Unlike CTGF, P2 had little effect on EMT induction including cytoskeleton remodeling and expression of alpha-smooth muscle actin (alpha-SMA) and E-cadherin, nor did it have effect on fibrogenic induction including alternation of extracellular matrix (ECM) proteins, collagen type I and IV at gene and protein levels. All data showed that P2 bound preferably on the surface of NRK-52E cells and inhibited the effect of CTGF on EMT induction and cell fibrogenesis, probably by occupying the binding sites of CTGF within its potential receptors. Therefore, P2 may be used as a potential anti-fibrotic agent.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Actins / metabolism
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Amino Acid Sequence
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Animals
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Cadherins / metabolism
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Cell Differentiation / drug effects*
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Cell Line
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Collagen Type I / genetics
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Collagen Type I / metabolism
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Collagen Type IV / genetics
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Collagen Type IV / metabolism
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Connective Tissue Growth Factor
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Cytoskeleton / metabolism
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Epithelial Cells / cytology*
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Epithelial Cells / drug effects*
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Epithelial Cells / metabolism
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Humans
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Immediate-Early Proteins / chemistry
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Immediate-Early Proteins / pharmacology*
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Integrin alphaVbeta3 / metabolism
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Intercellular Signaling Peptides and Proteins / chemistry
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Intercellular Signaling Peptides and Proteins / pharmacology*
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Mesenchymal Stem Cells / cytology*
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Mesenchymal Stem Cells / metabolism
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Molecular Sequence Data
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Muscle, Smooth / metabolism
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Peptide Fragments / chemical synthesis
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Peptide Fragments / chemistry
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Peptide Fragments / pharmacology*
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Protein Binding
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Protein Subunits / metabolism
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Rats
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Spectrometry, Mass, Electrospray Ionization
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Transcription, Genetic / genetics
Substances
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Actins
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CCN2 protein, human
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CCN2 protein, rat
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Cadherins
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Collagen Type I
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Collagen Type IV
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Immediate-Early Proteins
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Integrin alphaVbeta3
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Intercellular Signaling Peptides and Proteins
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Peptide Fragments
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Protein Subunits
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Connective Tissue Growth Factor