Type XVIII collagen is essential for survival during acute liver injury in mice

Michael B. Duncan, Changqing Yang, Harikrishna Tanjore, Patrick M. Boyle, Doruk Keskin, Hikaru Sugimoto, Michael Zeisberg, Bjorn R. Olsen, Raghu Kalluri

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)942-951
Number of pages10
JournalDMM Disease Models and Mechanisms
Volume6
Issue number4
DOIs
StatePublished - Jul 1 2013

Fingerprint

Collagen Type XVIII
Liver
Wounds and Injuries
Extracellular Matrix
Hepatocytes
Integrins
Chemical and Drug Induced Liver Injury
Poisons
Recovery
Molecules
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Duncan, M. B., Yang, C., Tanjore, H., Boyle, P. M., Keskin, D., Sugimoto, H., ... Kalluri, R. (2013). Type XVIII collagen is essential for survival during acute liver injury in mice. DMM Disease Models and Mechanisms, 6(4), 942-951. https://doi.org/10.1242/dmm.011577

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.

In: DMM Disease Models and Mechanisms, Vol. 6, No. 4, 01.07.2013, p. 942-951.

Research output: Contribution to journalArticle

Duncan, MB, Yang, C, Tanjore, H, Boyle, PM, Keskin, D, Sugimoto, H, Zeisberg, M, Olsen, BR & Kalluri, R 2013, 'Type XVIII collagen is essential for survival during acute liver injury in mice', DMM Disease Models and Mechanisms, vol. 6, no. 4, pp. 942-951. https://doi.org/10.1242/dmm.011577
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. In: DMM Disease Models and Mechanisms. 2013 ; Vol. 6, No. 4. pp. 942-951.
@article{5c04165ad1ca4cf599eb0c153011b1db,
title = "Type XVIII collagen is essential for survival during acute liver injury in mice",
abstract = "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.",
author = "Duncan, {Michael B.} and Changqing Yang and Harikrishna Tanjore and Boyle, {Patrick M.} and Doruk Keskin and Hikaru Sugimoto and Michael Zeisberg and Olsen, {Bjorn R.} and Raghu Kalluri",
year = "2013",
month = "7",
day = "1",
doi = "10.1242/dmm.011577",
language = "English (US)",
volume = "6",
pages = "942--951",
journal = "DMM Disease Models and Mechanisms",
issn = "1754-8403",
publisher = "Company of Biologists Ltd",
number = "4",

}

TY - JOUR

T1 - Type XVIII collagen is essential for survival during acute liver injury in mice

AU - Duncan, Michael B.

AU - Yang, Changqing

AU - Tanjore, Harikrishna

AU - Boyle, Patrick M.

AU - Keskin, Doruk

AU - Sugimoto, Hikaru

AU - Zeisberg, Michael

AU - Olsen, Bjorn R.

AU - Kalluri, Raghu

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84880017436&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880017436&partnerID=8YFLogxK

U2 - 10.1242/dmm.011577

DO - 10.1242/dmm.011577

M3 - Article

C2 - 23580202

AN - SCOPUS:84880017436

VL - 6

SP - 942

EP - 951

JO - DMM Disease Models and Mechanisms

JF - DMM Disease Models and Mechanisms

SN - 1754-8403

IS - 4

ER -