Targeted ablation of ILK from the murine heart results in dilated cardiomyopathy and spontaneous heart failure

被引：135

作者：

White, Donald E.

Coutu, Pierre

Shi, Yan-Fen

Tardif, Jean-Claude

Nattel, Stanley

Arnaud, Rene St.

Dedhar, Shoukat

Muller, William J. ^{[1
]}

机构：

[1] McGill Univ, Dept Biochem, Montreal, PQ H3A 1A1, Canada

[2] McGill Univ, Dept Med, Montreal, PQ H3A 1A1, Canada

[3] Univ Montreal, Inst Heart, Montreal, PQ H1T 1C8, Canada

[4] Shriners Hosp Crippled Children, Montreal, PQ H3G 1A6, Canada

[5] Univ British Columbia, Dept Biochem, Vancouver, BC V5Z 1L3, Canada

[6] Univ British Columbia, BC Canc Agcy, Vancouver, BC V5Z 1L3, Canada

来源：

GENES & DEVELOPMENT | 2006年 / 20卷 / 17期

关键词：

integrin-linked kinase; ILK; integrin; cardiomyopathy;

D O I：

10.1101/gad.1458906

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

A requirement for integrin-mediated adhesion in cardiac physiology is revealed through targeted deletion of integrin associated genes in the murine heart. Here we show that targeted ablation of the integrin-linked kinase (ILK) expression results in spontaneous cardiomyopathy and heart failure by 6 wk of age. Deletion of ILK results in disaggregation of cardiomyocytes, associated with disruption of adhesion signaling through the beta 1-integrin/ FAK (focal adhesion kinase) complex. Importantly, the loss of ILK is accompanied by a reduction in cardiac Akt phosphorylation, which normally provides a protective response against stress. Together, these results suggest that ILK plays a central role in protecting the mammalian heart against cardiomyopathy and failure.

引用

收藏

页码：2355 / 2360

页数：6

相关论文

共 33 条

[1] Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair [J].

Bock-Marquette, I ;

Saxena, A ;

White, MD ;

DiMaio, JM ;

Srivastava, D .

NATURE, 2004, 432 (7016) :466-472

[2] Melusin, a muscle-specific integrin β1-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload [J].

Brancaccio, M ;

Fratta, L ;

Notte, A ;

Hirsch, E ;

Poulet, R ;

Guazzone, S ;

De Acetis, M ;

Vecchione, C ;

Marino, G ;

Altruda, F ;

Silengo, L ;

Tarone, G ;

Lembo, G .

NATURE MEDICINE, 2003, 9 (01) :68-75

[3] Role of the integrin-linked kinase/PINCH1/alpha-parvin complex in cardiac myocyte hypertrophy [J].

Chen, H ;

Huang, XYN ;

Yan, W ;

Chen, K ;

Guo, LD ;

Tummalapali, L ;

Dedhar, S ;

St-Arnaud, R ;

Wu, CY ;

Sepulveda, JL .

LABORATORY INVESTIGATION, 2005, 85 (11) :1342-1356

[4] The integrin-linked kinase regulates the cyclin D1 gene through glycogen synthase kinase 3β and cAMP-responsive element-binding protein-dependent pathways [J].

D'Amico, M ;

Hulit, J ;

Amanatullah, DF ;

Zafonte, BT ;

Albanese, C ;

Bouzahzah, B ;

Fu, MF ;

Augenlicht, LH ;

Donehower, LA ;

Takemaru, KI ;

Moon, RT ;

Davis, R ;

Lisanti, MP ;

Shtutman, M ;

Zhurinsky, J ;

Ben-Ze'ev, A ;

Troussard, AA ;

Dedhar, S ;

Pestell, RG .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (42) :32649-32657

[5] Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase [J].

Delcommenne, M ;

Tan, C ;

Gray, V ;

Rue, L ;

Woodgett, J ;

Dedhar, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (19) :11211-11216

[6] Integrin-linked kinase: A cancer therapeutic target unique among its ILK [J].

Hannigan, G ;

Troussard, AA ;

Dedhar, S .

NATURE REVIEWS CANCER, 2005, 5 (01) :51-63

[7] Regulation of cell adhesion and anchorage-dependent growth by a new beta(1)-integrin-linked protein kinase [J].

Hannigan, GE ;

LeungHagesteijn, C ;

FitzGibbon, L ;

Coppolino, MG ;

Radeva, G ;

Filmus, J ;

Bell, JC ;

Dedhar, S .

NATURE, 1996, 379 (6560) :91-96

[8] The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy [J].

Knöll, R ;

Hoshijima, M ;

Hoffman, HM ;

Person, V ;

Lorenzen-Schmidt, I ;

Bang, ML ;

Hayashi, T ;

Shiga, N ;

Yasukawa, H ;

Schaper, W ;

McKenna, W ;

Yokoyama, M ;

Schork, NJ ;

Omens, JH ;

McCulloch, AD ;

Kimura, A ;

Gregorio, CC ;

Poller, W ;

Schaper, J ;

Schultheiss, HP ;

Chien, KR .

CELL, 2002, 111 (07) :943-955

[9] Identification and characterization of a mouse protein kinase that is highly homologous to human integrin-linked kinase [J].

Li, FG ;

Liu, JG ;

Mayne, R ;

Wu, CY .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1997, 1358 (03) :215-220

[10] Targeted deletion of integrin-linked kinase reveals a role in T-cell chemotaxis and survival [J].

Liu, E ;

Sinha, S ;

Williams, C ;

Cyrille, M ;

Heller, E ;

Snapper, SB ;

Georgopoulos, K ;

St-Arnaud, R ;

Force, T ;

Dedhar, S ;

Gerszten, RE .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (24) :11145-11155

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