Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways
► Akt, ERK, and p38 pathways are involved in SDF-1-induced hUCB-MSC migration. ► SDF-1 activates Akt, ERK, and p38 signal transduction pathways in hUCB-MSCs. ► Knockdown of Akt, ERK, and p38 inhibits SDF-1-induced migration of hUCB-MSCs. ► PI3K, ERK, and p38 inhibitors reduce SDF-1-induced actinpoly...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2010-07, Vol.398 (1), p.105-110 |
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| creator | Ryu, Chung Heon Park, Soon A Kim, Seong Muk Lim, Jung Yeon Jeong, Chang Hyun Jun, Jin Ae Oh, Ji Hyeon Park, Sun Hwa Oh, Won-il Jeun, Sin-Soo |
| description | ► Akt, ERK, and p38 pathways are involved in SDF-1-induced hUCB-MSC migration. ► SDF-1 activates Akt, ERK, and p38 signal transduction pathways in hUCB-MSCs. ► Knockdown of Akt, ERK, and p38 inhibits SDF-1-induced migration of hUCB-MSCs. ► PI3K, ERK, and p38 inhibitors reduce SDF-1-induced actinpolymerization in hUCB-MSCs.
Human mesenchymal stem cells (hMSCs) have been used for cell-based therapies in degenerative disease and as vehicles for delivering therapeutic genes to sites of injury and tumors. Recently, umbilical cord blood (UCB) was identified as a source for MSCs, and human UCB-derived MSCs (hUCB-MSCs) can serve as an alternative source of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, migration signaling pathways required for homing and recruitment of hUCB-MSCs are not fully understood. Stromal cell-derived factor-1 (SDF-1), a ligand for the CXCR4 chemokine receptor, plays a pivotal role in mobilization and homing of stem cells and modulates different biological responses in various stem cells. In this study, expression of CXCR4 in hUCB-MSCs was studied by western blot analysis and the functional role of SDF-1 was assessed. SDF-1 induced the migration of hUCB-MSCs in a dose-dependent manner. The induced migration was inhibited by the CXCR4-specific peptide antagonist (AMD3100) and by inhibitors of phosphoinositide 3-kinase (LY294002), mitogen-activated protein kinase/extracellular signal related kinase (PD98059) and p38MAPK inhibitor (SB203580). hUCB-MSCs treated with SDF-1 displayed increased phosphorylation of Akt, ERK and p38, which were inhibited by AMD3100. Small-interfering RNA-mediated knock-down of Akt, ERK and p38 blocked SDF-1 induced hUCB-MSC migration. In addition, SDF-1-induced actin polymerization was also blocked by these inhibitors. Taken together, these results demonstrate that Akt, ERK and p38 signal transduction pathways may be involved in SDF-1-mediated migration of hUCB-MSCs. |
| doi_str_mv | 10.1016/j.bbrc.2010.06.043 |
| format | Article |
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Human mesenchymal stem cells (hMSCs) have been used for cell-based therapies in degenerative disease and as vehicles for delivering therapeutic genes to sites of injury and tumors. Recently, umbilical cord blood (UCB) was identified as a source for MSCs, and human UCB-derived MSCs (hUCB-MSCs) can serve as an alternative source of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, migration signaling pathways required for homing and recruitment of hUCB-MSCs are not fully understood. Stromal cell-derived factor-1 (SDF-1), a ligand for the CXCR4 chemokine receptor, plays a pivotal role in mobilization and homing of stem cells and modulates different biological responses in various stem cells. In this study, expression of CXCR4 in hUCB-MSCs was studied by western blot analysis and the functional role of SDF-1 was assessed. SDF-1 induced the migration of hUCB-MSCs in a dose-dependent manner. The induced migration was inhibited by the CXCR4-specific peptide antagonist (AMD3100) and by inhibitors of phosphoinositide 3-kinase (LY294002), mitogen-activated protein kinase/extracellular signal related kinase (PD98059) and p38MAPK inhibitor (SB203580). hUCB-MSCs treated with SDF-1 displayed increased phosphorylation of Akt, ERK and p38, which were inhibited by AMD3100. Small-interfering RNA-mediated knock-down of Akt, ERK and p38 blocked SDF-1 induced hUCB-MSC migration. In addition, SDF-1-induced actin polymerization was also blocked by these inhibitors. Taken together, these results demonstrate that Akt, ERK and p38 signal transduction pathways may be involved in SDF-1-mediated migration of hUCB-MSCs.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2010.06.043</identifier><identifier>PMID: 20558135</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Cell Movement ; Chemokine CXCL12 - physiology ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Humans ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - physiology ; p38 Mitogen-Activated Protein Kinases - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; Receptors, CXCR4 - physiology ; Signal Transduction ; Stromal cell-derived factor-1 ; Stromal Cells - physiology ; Umbilical Cord - cytology ; Umbilical cord blood</subject><ispartof>Biochemical and biophysical research communications, 2010-07, Vol.398 (1), p.105-110</ispartof><rights>2010 Elsevier Inc.</rights><rights>Copyright 2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c355t-193c497cb18edb9239cab9c10468b5f356863561756fa0da32c779b6a6ba62433</citedby><cites>FETCH-LOGICAL-c355t-193c497cb18edb9239cab9c10468b5f356863561756fa0da32c779b6a6ba62433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2010.06.043$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20558135$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ryu, Chung Heon</creatorcontrib><creatorcontrib>Park, Soon A</creatorcontrib><creatorcontrib>Kim, Seong Muk</creatorcontrib><creatorcontrib>Lim, Jung Yeon</creatorcontrib><creatorcontrib>Jeong, Chang Hyun</creatorcontrib><creatorcontrib>Jun, Jin Ae</creatorcontrib><creatorcontrib>Oh, Ji Hyeon</creatorcontrib><creatorcontrib>Park, Sun Hwa</creatorcontrib><creatorcontrib>Oh, Won-il</creatorcontrib><creatorcontrib>Jeun, Sin-Soo</creatorcontrib><title>Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>► Akt, ERK, and p38 pathways are involved in SDF-1-induced hUCB-MSC migration. ► SDF-1 activates Akt, ERK, and p38 signal transduction pathways in hUCB-MSCs. ► Knockdown of Akt, ERK, and p38 inhibits SDF-1-induced migration of hUCB-MSCs. ► PI3K, ERK, and p38 inhibitors reduce SDF-1-induced actinpolymerization in hUCB-MSCs.
Human mesenchymal stem cells (hMSCs) have been used for cell-based therapies in degenerative disease and as vehicles for delivering therapeutic genes to sites of injury and tumors. Recently, umbilical cord blood (UCB) was identified as a source for MSCs, and human UCB-derived MSCs (hUCB-MSCs) can serve as an alternative source of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, migration signaling pathways required for homing and recruitment of hUCB-MSCs are not fully understood. Stromal cell-derived factor-1 (SDF-1), a ligand for the CXCR4 chemokine receptor, plays a pivotal role in mobilization and homing of stem cells and modulates different biological responses in various stem cells. In this study, expression of CXCR4 in hUCB-MSCs was studied by western blot analysis and the functional role of SDF-1 was assessed. SDF-1 induced the migration of hUCB-MSCs in a dose-dependent manner. The induced migration was inhibited by the CXCR4-specific peptide antagonist (AMD3100) and by inhibitors of phosphoinositide 3-kinase (LY294002), mitogen-activated protein kinase/extracellular signal related kinase (PD98059) and p38MAPK inhibitor (SB203580). hUCB-MSCs treated with SDF-1 displayed increased phosphorylation of Akt, ERK and p38, which were inhibited by AMD3100. Small-interfering RNA-mediated knock-down of Akt, ERK and p38 blocked SDF-1 induced hUCB-MSC migration. In addition, SDF-1-induced actin polymerization was also blocked by these inhibitors. Taken together, these results demonstrate that Akt, ERK and p38 signal transduction pathways may be involved in SDF-1-mediated migration of hUCB-MSCs.</description><subject>Cell Movement</subject><subject>Chemokine CXCL12 - physiology</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Humans</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - physiology</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptors, CXCR4 - physiology</subject><subject>Signal Transduction</subject><subject>Stromal cell-derived factor-1</subject><subject>Stromal Cells - physiology</subject><subject>Umbilical Cord - cytology</subject><subject>Umbilical cord blood</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UcFu1DAQtRAV3RZ-gAPyjUuzHceJk0hcqlUpiFZIFUi9WWPH6XpJ4sV2tuwP8Z11ui1HLjPSmzdPM-8R8p7BkgET55ulUl4vc0gAiCUU_BVZMGggyxkUr8kCAESWN-zumJyEsAFgrBDNG3KcQ1nWjJcL8vfG3nuM1o3UdXQ9DTjSaVC2txp7qp1vqeqda-lgghn1ej8kOEQzUG36PiS4tRhNYu0T7N08nidZa7zdJbxDHZ3P2PnqbnVbUPxjA91ZpBe_4hm9vP12RnFs6ZbXNNj7MW1Hj2NoJ_100xbj-gH34S056rAP5t1zPyU_P1_-WH3Jrr9ffV1dXGeal2XMWMN10VRasdq0qsl5o1E1OrkhalV2vBS1SIVVpegQWuS5rqpGCRQKRV5wfko-HnS33v2eTIhysGH-B0fjpiArXgDwkkFi5gem9i4Ebzq59XZAv5cM5ByP3Mg5HjnHI0FIeJL_8Cw_qeTcv5WXPBLh04Fg0pM7a7wM2ibfk8ve6ChbZ_-n_whdCqHP</recordid><startdate>20100716</startdate><enddate>20100716</enddate><creator>Ryu, Chung Heon</creator><creator>Park, Soon A</creator><creator>Kim, Seong Muk</creator><creator>Lim, Jung Yeon</creator><creator>Jeong, Chang Hyun</creator><creator>Jun, Jin Ae</creator><creator>Oh, Ji Hyeon</creator><creator>Park, Sun Hwa</creator><creator>Oh, Won-il</creator><creator>Jeun, Sin-Soo</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100716</creationdate><title>Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways</title><author>Ryu, Chung Heon ; Park, Soon A ; Kim, Seong Muk ; Lim, Jung Yeon ; Jeong, Chang Hyun ; Jun, Jin Ae ; Oh, Ji Hyeon ; Park, Sun Hwa ; Oh, Won-il ; Jeun, Sin-Soo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c355t-193c497cb18edb9239cab9c10468b5f356863561756fa0da32c779b6a6ba62433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Cell Movement</topic><topic>Chemokine CXCL12 - physiology</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Humans</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - physiology</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptors, CXCR4 - physiology</topic><topic>Signal Transduction</topic><topic>Stromal cell-derived factor-1</topic><topic>Stromal Cells - physiology</topic><topic>Umbilical Cord - cytology</topic><topic>Umbilical cord blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ryu, Chung Heon</creatorcontrib><creatorcontrib>Park, Soon A</creatorcontrib><creatorcontrib>Kim, Seong Muk</creatorcontrib><creatorcontrib>Lim, Jung Yeon</creatorcontrib><creatorcontrib>Jeong, Chang Hyun</creatorcontrib><creatorcontrib>Jun, Jin Ae</creatorcontrib><creatorcontrib>Oh, Ji Hyeon</creatorcontrib><creatorcontrib>Park, Sun Hwa</creatorcontrib><creatorcontrib>Oh, Won-il</creatorcontrib><creatorcontrib>Jeun, Sin-Soo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ryu, Chung Heon</au><au>Park, Soon A</au><au>Kim, Seong Muk</au><au>Lim, Jung Yeon</au><au>Jeong, Chang Hyun</au><au>Jun, Jin Ae</au><au>Oh, Ji Hyeon</au><au>Park, Sun Hwa</au><au>Oh, Won-il</au><au>Jeun, Sin-Soo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2010-07-16</date><risdate>2010</risdate><volume>398</volume><issue>1</issue><spage>105</spage><epage>110</epage><pages>105-110</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>► Akt, ERK, and p38 pathways are involved in SDF-1-induced hUCB-MSC migration. ► SDF-1 activates Akt, ERK, and p38 signal transduction pathways in hUCB-MSCs. ► Knockdown of Akt, ERK, and p38 inhibits SDF-1-induced migration of hUCB-MSCs. ► PI3K, ERK, and p38 inhibitors reduce SDF-1-induced actinpolymerization in hUCB-MSCs.
Human mesenchymal stem cells (hMSCs) have been used for cell-based therapies in degenerative disease and as vehicles for delivering therapeutic genes to sites of injury and tumors. Recently, umbilical cord blood (UCB) was identified as a source for MSCs, and human UCB-derived MSCs (hUCB-MSCs) can serve as an alternative source of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, migration signaling pathways required for homing and recruitment of hUCB-MSCs are not fully understood. Stromal cell-derived factor-1 (SDF-1), a ligand for the CXCR4 chemokine receptor, plays a pivotal role in mobilization and homing of stem cells and modulates different biological responses in various stem cells. In this study, expression of CXCR4 in hUCB-MSCs was studied by western blot analysis and the functional role of SDF-1 was assessed. SDF-1 induced the migration of hUCB-MSCs in a dose-dependent manner. The induced migration was inhibited by the CXCR4-specific peptide antagonist (AMD3100) and by inhibitors of phosphoinositide 3-kinase (LY294002), mitogen-activated protein kinase/extracellular signal related kinase (PD98059) and p38MAPK inhibitor (SB203580). hUCB-MSCs treated with SDF-1 displayed increased phosphorylation of Akt, ERK and p38, which were inhibited by AMD3100. Small-interfering RNA-mediated knock-down of Akt, ERK and p38 blocked SDF-1 induced hUCB-MSC migration. In addition, SDF-1-induced actin polymerization was also blocked by these inhibitors. Taken together, these results demonstrate that Akt, ERK and p38 signal transduction pathways may be involved in SDF-1-mediated migration of hUCB-MSCs.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20558135</pmid><doi>10.1016/j.bbrc.2010.06.043</doi><tpages>6</tpages></addata></record> |
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| subjects | Cell Movement Chemokine CXCL12 - physiology Extracellular Signal-Regulated MAP Kinases - metabolism Humans Mesenchymal stem cells Mesenchymal Stromal Cells - physiology p38 Mitogen-Activated Protein Kinases - metabolism Proto-Oncogene Proteins c-akt - metabolism Receptors, CXCR4 - physiology Signal Transduction Stromal cell-derived factor-1 Stromal Cells - physiology Umbilical Cord - cytology Umbilical cord blood |
| title | Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways |
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