Type XVIII collagen is essential for survival during acute liver injury in mice
The regenerative response to drug- and toxin-induced liver injury induces changes to the hepatic stroma, including the extracellular matrix. Although the extracellular matrix is known to undergo changes during the injury response, its impact on maintaining hepatocyte function and viability in this p...
| Autores principales: | , , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | en_US |
| Publicado: |
Company of Biologists, Ltd.
2014
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| Acceso en línea: | http://hdl.handle.net/1721.1/90967 |
| _version_ | 1826204868517298176 |
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| author | Duncan, Michael B. Yang, Changqing Tanjore, Harikrishna Boyle, Patrick M. Keskin, Doruk Sugimoto, Hikaru Zeisberg, Michael Olsen, Bjorn R. Kalluri, Raghu |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Duncan, Michael B. Yang, Changqing Tanjore, Harikrishna Boyle, Patrick M. Keskin, Doruk Sugimoto, Hikaru Zeisberg, Michael Olsen, Bjorn R. Kalluri, Raghu |
| author_sort | Duncan, Michael B. |
| collection | MIT |
| description | The regenerative response to drug- and toxin-induced liver injury induces changes to the hepatic stroma, including the extracellular matrix. Although the extracellular matrix is known to undergo changes during the injury response, its impact on maintaining hepatocyte function and viability in this process remains largely unknown. We demonstrate that recovery from toxin-mediated injury is impaired in mice deficient in a key liver extracellular matrix molecule, type XVIII collagen, and results in rapid death. The type-XVIII-collagen-dependent response to liver injury is mediated by survival signals induced by α1β1 integrin, integrin linked kinase and the Akt pathway, and mice deficient in either α1β1 integrin or hepatocyte integrin linked kinase also succumb to toxic liver injury. These findings demonstrate that type XVIII collagen is an important functional component of the liver matrix microenvironment and is crucial for hepatocyte survival during injury and stress. |
| first_indexed | 2024-09-23T13:02:39Z |
| format | Article |
| id | mit-1721.1/90967 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:02:39Z |
| publishDate | 2014 |
| publisher | Company of Biologists, Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/909672022-09-28T11:41:25Z Type XVIII collagen is essential for survival during acute liver injury in mice Duncan, Michael B. Yang, Changqing Tanjore, Harikrishna Boyle, Patrick M. Keskin, Doruk Sugimoto, Hikaru Zeisberg, Michael Olsen, Bjorn R. Kalluri, Raghu Harvard University--MIT Division of Health Sciences and Technology Kalluri, Raghu The regenerative response to drug- and toxin-induced liver injury induces changes to the hepatic stroma, including the extracellular matrix. Although the extracellular matrix is known to undergo changes during the injury response, its impact on maintaining hepatocyte function and viability in this process remains largely unknown. We demonstrate that recovery from toxin-mediated injury is impaired in mice deficient in a key liver extracellular matrix molecule, type XVIII collagen, and results in rapid death. The type-XVIII-collagen-dependent response to liver injury is mediated by survival signals induced by α1β1 integrin, integrin linked kinase and the Akt pathway, and mice deficient in either α1β1 integrin or hepatocyte integrin linked kinase also succumb to toxic liver injury. These findings demonstrate that type XVIII collagen is an important functional component of the liver matrix microenvironment and is crucial for hepatocyte survival during injury and stress. National Institutes of Health (U.S.) (NIH grant AA013913) National Institutes of Health (U.S.) (NIH grant DK 55001) National Institutes of Health (U.S.) (NIH grant CA 125550) National Institutes of Health (U.S.) (NIH grant CA 155370) National Institutes of Health (U.S.) (NIH grant CA 151925) National Institutes of Health (U.S.) (NIH grant DK 081576) National Institutes of Health (U.S.) (NIH grant AR 36820) UNCF-Merck Postdoctoral Fellowship Beth Isreal Deaconess Medical Center (Cancer Biology Training Grant (5 T32 CA081156-08)) Beth Isreal Deaconess Medical Center (Cardiovascular Research Training Program (5 T32 HL007374-30)) 2014-10-17T17:15:16Z 2014-10-17T17:15:16Z 2013-04 Article http://purl.org/eprint/type/JournalArticle 1754-8403 1754-8411 http://hdl.handle.net/1721.1/90967 Duncan, M. B., C. Yang, H. Tanjore, P. M. Boyle, D. Keskin, H. Sugimoto, M. Zeisberg, B. R. Olsen, and R. Kalluri. “Type XVIII Collagen Is Essential for Survival During Acute Liver Injury in Mice.” Disease Models & Mechanisms 6, no. 4 (April 4, 2013): 942–951. en_US http://dx.doi.org/10.1242/dmm.011577 Disease Models & Mechanisms Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf Company of Biologists, Ltd. Company of Biologists |
| spellingShingle | Duncan, Michael B. Yang, Changqing Tanjore, Harikrishna Boyle, Patrick M. Keskin, Doruk Sugimoto, Hikaru Zeisberg, Michael Olsen, Bjorn R. Kalluri, Raghu Type XVIII collagen is essential for survival during acute liver injury in mice |
| title | Type XVIII collagen is essential for survival during acute liver injury in mice |
| title_full | Type XVIII collagen is essential for survival during acute liver injury in mice |
| title_fullStr | Type XVIII collagen is essential for survival during acute liver injury in mice |
| title_full_unstemmed | Type XVIII collagen is essential for survival during acute liver injury in mice |
| title_short | Type XVIII collagen is essential for survival during acute liver injury in mice |
| title_sort | type xviii collagen is essential for survival during acute liver injury in mice |
| url | http://hdl.handle.net/1721.1/90967 |
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