Homologous peptide of connective tissue growth factor ameliorates epithelial to mesenchymal transition of tubular epithelial cells

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) wh...

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Veröffentlicht in:Cytokine (Philadelphia, Pa.) Pa.), 2006-10, Vol.36 (1), p.35-44
Hauptverfasser: Shi, Yujun, Tu, Zhidan, Wang, Wei, Li, Qing, Ye, Feng, Wang, Jinjing, Qiu, Jing, Zhang, Li, Bu, Hong, Li, Youping
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container_issue 1
container_start_page 35
container_title Cytokine (Philadelphia, Pa.)
container_volume 36
creator Shi, Yujun
Tu, Zhidan
Wang, Wei
Li, Qing
Ye, Feng
Wang, Jinjing
Qiu, Jing
Zhang, Li
Bu, Hong
Li, Youping
description 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 αvβ3 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 α-smooth muscle actin (α-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.
doi_str_mv 10.1016/j.cyto.2006.10.009
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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 αvβ3 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 α-smooth muscle actin (α-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. 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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 αvβ3 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 α-smooth muscle actin (α-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. 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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 αvβ3 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 α-smooth muscle actin (α-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. 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subjects Actins - genetics
Actins - metabolism
Amino Acid Sequence
Animals
Cadherins - metabolism
Cell Differentiation - drug effects
Cell Line
Collagen Type I - genetics
Collagen Type I - metabolism
Collagen Type IV - genetics
Collagen Type IV - metabolism
Connective Tissue Growth Factor
Cytoskeleton - metabolism
Epithelial Cells - cytology
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Epithelial–mesenchymal transition
Fibrosis
Humans
Immediate-Early Proteins - chemistry
Immediate-Early Proteins - pharmacology
Integrin alphaVbeta3 - metabolism
Intercellular Signaling Peptides and Proteins - chemistry
Intercellular Signaling Peptides and Proteins - pharmacology
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - metabolism
Molecular Sequence Data
Muscle, Smooth - metabolism
Peptide
Peptide Fragments - chemical synthesis
Peptide Fragments - chemistry
Peptide Fragments - pharmacology
Protein Binding
Protein Subunits - metabolism
Rats
Spectrometry, Mass, Electrospray Ionization
Transcription, Genetic - genetics
Tubular epithelial cells
title Homologous peptide of connective tissue growth factor ameliorates epithelial to mesenchymal transition of tubular epithelial cells
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