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Abi3bp Is a Multifunctional Autocrine/Paracrine Factor that Regulates Mesenchymal Stem Cell Biology
Mesenchymal stem cells (MSCs) transplanted into injured myocardium promote repair through paracrine mechanisms. We have previously shown that MSCs over‐expressing AKT1 (Akt‐MSCs) exhibit enhanced properties for cardiac repair. In this study, we investigated the relevance of Abi3bp toward MSC biology...
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| Published in: | Stem cells (Dayton, Ohio) Ohio), 2013-08, Vol.31 (8), p.1669-1682 |
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| cites | cdi_FETCH-LOGICAL-c4766-bd9dddc6c895b40880836f38d14c58f9c37033720fa86e1edfa8c0b4ab51c9bc3 |
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| container_title | Stem cells (Dayton, Ohio) |
| container_volume | 31 |
| creator | Hodgkinson, Conrad P. Naidoo, Vinogran Patti, Karl G. Gomez, Jose A. Schmeckpeper, Jeffrey Zhang, Zhiping Davis, Bryce Pratt, Richard E. Mirotsou, Maria Dzau, Victor J. |
| description | Mesenchymal stem cells (MSCs) transplanted into injured myocardium promote repair through paracrine mechanisms. We have previously shown that MSCs over‐expressing AKT1 (Akt‐MSCs) exhibit enhanced properties for cardiac repair. In this study, we investigated the relevance of Abi3bp toward MSC biology. Abi3bp formed extracellular deposits with expression controlled by Akt1 and ubiquitin‐mediated degradation. Abi3bp knockdown/knockout stabilized focal adhesions and promoted stress‐fiber formation. Furthermore, MSCs from Abi3bp knockout mice displayed severe deficiencies in osteogenic and adipogenic differentiation. Knockout or stable knockdown of Abi3bp increased MSC and Akt‐MSC proliferation, promoting S‐phase entry via cyclin‐d1, ERK1/2, and Src. Upon Abi3bp binding to integrin‐β1 Src associated with paxillin which inhibited proliferation. In vivo, Abi3bp knockout increased MSC number and proliferation in bone marrow, lung, and liver. In summary, we have identified a novel extracellular matrix protein necessary for the switch from proliferation to differentiation in MSCs. STEM Cells
2013;31:1669–1682 |
| doi_str_mv | 10.1002/stem.1416 |
| format | article |
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2013;31:1669–1682</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1002/stem.1416</identifier><identifier>PMID: 23666637</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Autocrine Communication ; Bone marrow ; Carrier Proteins - metabolism ; Carrier Proteins - physiology ; Cell Communication - physiology ; Cell Differentiation - physiology ; Cell Growth Processes - physiology ; Cell Movement - physiology ; Cell signaling ; Extracellular matrix ; Integrin ; Male ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - metabolism ; Mesenchymal Stromal Cells - physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Paracrine Communication ; Proto-Oncogene Proteins c-akt - metabolism ; Stem cells ; Transfection ; Ubiquitin - metabolism</subject><ispartof>Stem cells (Dayton, Ohio), 2013-08, Vol.31 (8), p.1669-1682</ispartof><rights>Copyright © 2013 AlphaMed Press</rights><rights>Copyright © 2013 AlphaMed Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4766-bd9dddc6c895b40880836f38d14c58f9c37033720fa86e1edfa8c0b4ab51c9bc3</citedby><cites>FETCH-LOGICAL-c4766-bd9dddc6c895b40880836f38d14c58f9c37033720fa86e1edfa8c0b4ab51c9bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23666637$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hodgkinson, Conrad P.</creatorcontrib><creatorcontrib>Naidoo, Vinogran</creatorcontrib><creatorcontrib>Patti, Karl G.</creatorcontrib><creatorcontrib>Gomez, Jose A.</creatorcontrib><creatorcontrib>Schmeckpeper, Jeffrey</creatorcontrib><creatorcontrib>Zhang, Zhiping</creatorcontrib><creatorcontrib>Davis, Bryce</creatorcontrib><creatorcontrib>Pratt, Richard E.</creatorcontrib><creatorcontrib>Mirotsou, Maria</creatorcontrib><creatorcontrib>Dzau, Victor J.</creatorcontrib><title>Abi3bp Is a Multifunctional Autocrine/Paracrine Factor that Regulates Mesenchymal Stem Cell Biology</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>Mesenchymal stem cells (MSCs) transplanted into injured myocardium promote repair through paracrine mechanisms. We have previously shown that MSCs over‐expressing AKT1 (Akt‐MSCs) exhibit enhanced properties for cardiac repair. In this study, we investigated the relevance of Abi3bp toward MSC biology. Abi3bp formed extracellular deposits with expression controlled by Akt1 and ubiquitin‐mediated degradation. Abi3bp knockdown/knockout stabilized focal adhesions and promoted stress‐fiber formation. Furthermore, MSCs from Abi3bp knockout mice displayed severe deficiencies in osteogenic and adipogenic differentiation. Knockout or stable knockdown of Abi3bp increased MSC and Akt‐MSC proliferation, promoting S‐phase entry via cyclin‐d1, ERK1/2, and Src. Upon Abi3bp binding to integrin‐β1 Src associated with paxillin which inhibited proliferation. In vivo, Abi3bp knockout increased MSC number and proliferation in bone marrow, lung, and liver. In summary, we have identified a novel extracellular matrix protein necessary for the switch from proliferation to differentiation in MSCs. STEM Cells
2013;31:1669–1682</description><subject>Animals</subject><subject>Autocrine Communication</subject><subject>Bone marrow</subject><subject>Carrier Proteins - metabolism</subject><subject>Carrier Proteins - physiology</subject><subject>Cell Communication - physiology</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Growth Processes - physiology</subject><subject>Cell Movement - physiology</subject><subject>Cell signaling</subject><subject>Extracellular matrix</subject><subject>Integrin</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Mesenchymal Stromal Cells - physiology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Paracrine Communication</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Stem cells</subject><subject>Transfection</subject><subject>Ubiquitin - metabolism</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqNkV9rFDEUxYMotrY--AUk4Et92G4yyeTPi7AurRa6WGx9DplMZjclM1mTTGW_vZluLbYgeF_uhfzu4dwcAN5hdIoRquYp2_4UU8xegENcUzmjEouXZUaMzWok5QF4k9ItQpjWQrwGBxVhpQg_BGbRONJs4UWCGq5Gn103Dia7MGgPF2MOJrrBzq901PcTPNcmhwjzRmf43a5Hr7NNcGWTHcxm15et6-IGLq338LMLPqx3x-BVp32ybx_6Efhxfnaz_Dq7_PblYrm4nBnKi9GmlW3bGmaErBuKhECCsI6IFlNTi04awhEhvEKdFsxi25ZuUEN1U2MjG0OOwKe97nZsetsaO-SovdpG1-u4U0E79fRlcBu1DneKcF5LgYrAyYNADD9Hm7LqXTLlEj3YMCaFKaGIVBz_F0oqRgXDBf3wDL0NYyz_O1EVJ0TwaqI-7ikTQ0rRdo--MVJTympKWU0pF_b934c-kn9iLcB8D_xy3u7-raSub85W95K_Ab5ssqY</recordid><startdate>201308</startdate><enddate>201308</enddate><creator>Hodgkinson, Conrad P.</creator><creator>Naidoo, Vinogran</creator><creator>Patti, Karl G.</creator><creator>Gomez, Jose A.</creator><creator>Schmeckpeper, Jeffrey</creator><creator>Zhang, Zhiping</creator><creator>Davis, Bryce</creator><creator>Pratt, Richard E.</creator><creator>Mirotsou, Maria</creator><creator>Dzau, Victor J.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Oxford University Press</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>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201308</creationdate><title>Abi3bp Is a Multifunctional Autocrine/Paracrine Factor that Regulates Mesenchymal Stem Cell Biology</title><author>Hodgkinson, Conrad P. ; 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We have previously shown that MSCs over‐expressing AKT1 (Akt‐MSCs) exhibit enhanced properties for cardiac repair. In this study, we investigated the relevance of Abi3bp toward MSC biology. Abi3bp formed extracellular deposits with expression controlled by Akt1 and ubiquitin‐mediated degradation. Abi3bp knockdown/knockout stabilized focal adhesions and promoted stress‐fiber formation. Furthermore, MSCs from Abi3bp knockout mice displayed severe deficiencies in osteogenic and adipogenic differentiation. Knockout or stable knockdown of Abi3bp increased MSC and Akt‐MSC proliferation, promoting S‐phase entry via cyclin‐d1, ERK1/2, and Src. Upon Abi3bp binding to integrin‐β1 Src associated with paxillin which inhibited proliferation. In vivo, Abi3bp knockout increased MSC number and proliferation in bone marrow, lung, and liver. In summary, we have identified a novel extracellular matrix protein necessary for the switch from proliferation to differentiation in MSCs. STEM Cells
2013;31:1669–1682</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>23666637</pmid><doi>10.1002/stem.1416</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford Journals Online |
| subjects | Animals Autocrine Communication Bone marrow Carrier Proteins - metabolism Carrier Proteins - physiology Cell Communication - physiology Cell Differentiation - physiology Cell Growth Processes - physiology Cell Movement - physiology Cell signaling Extracellular matrix Integrin Male Mesenchymal Stem Cell Transplantation - methods Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - metabolism Mesenchymal Stromal Cells - physiology Mice Mice, Inbred C57BL Mice, Knockout Paracrine Communication Proto-Oncogene Proteins c-akt - metabolism Stem cells Transfection Ubiquitin - metabolism |
| title | Abi3bp Is a Multifunctional Autocrine/Paracrine Factor that Regulates Mesenchymal Stem Cell Biology |
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