| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Department of Biochemistry and Biophysics and the Center for Cancer Biology and Nutrition,* Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston; and the Graduate School of Biomedical Sciences, The University of Texas-Houston Health Science Center, Houston, Texas
Carbon tetrachloride (CCl4) intoxification in rodents is a commonly used model of both acute and chronic liver injury. Recently, we showed that mice in which FGFR4 was ablated from the germline exhibited elevated cholesterol metabolism and bile acid synthesis coincident with unrepressed levels of cytochrome P450 7A (CYP7A), the rate-limiting enzyme in cholesterol disposal. Of the four fibroblast growth factor (FGF) receptor genes expressed in adult liver, FGFR4 is expressed specifically in mature hepatocytes. To determine whether FGFR4 plays a broader role in liver-specific metabolic functions, we examined the impact of both acute and chronic exposure to CCl4 in FGFR4-deficient mice. Following acute CCl4 exposure, the FGFR4-deficient mice exhibited accelerated liver injury, a significant increase in liver mass and delayed hepatolobular repair. Chronic CCl4 exposure resulted in severe fibrosis in livers of FGFR4-deficient mice compared to normal mice. Analysis at both mRNA and protein levels indicated an 8-hour delay in FGFR4-deficient mice in the down-regulation of cytochrome P450 2E1 (CYP2E1) protein, the major enzyme whose products underlie CCl4-induced injury. These results show that hepatocyte FGFR4 protects against acute and chronic insult to the liver and prevents accompanying fibrosis. The results show that FGFR4 acts by promotion of processes that restore hepatolobular architecture rather than cellularity while limiting damage due to prolonged CYP2E1 activity.
This article has been cited by other articles:
 |
|
 |
|
  P. Chen, C. Li, W. Pang, Y. Zhao, W. Dong, S. Wang, and J. Zhang The Protective Role of Per2 Against Carbon Tetrachloride-Induced Hepatotoxicity Am. J. Pathol., January 1, 2009; 174(1): 63 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Huang, C. Yu, C. Jin, M. Kobayashi, C. A. Bowles, F. Wang, and W. L. McKeehan Ectopic Activity of Fibroblast Growth Factor Receptor 1 in Hepatocytes Accelerates Hepatocarcinogenesis by Driving Proliferation and Vascular Endothelial Growth Factor-Induced Angiogenesis Cancer Res., February 1, 2006; 66(3): 1481 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zhao, G. Caretti, S. Mitchell, W. L. McKeehan, A. L. Boskey, L. M. Pachman, V. Sartorelli, and E. P. Hoffman Fgfr4 Is Required for Effective Muscle Regeneration in Vivo: DELINEATION OF A MyoD-Tead2-Fgfr4 TRANSCRIPTIONAL PATHWAY J. Biol. Chem., January 6, 2006; 281(1): 429 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Yu, F. Wang, C. Jin, X. Huang, and W. L. McKeehan Independent Repression of Bile Acid Synthesis and Activation of c-Jun N-terminal Kinase (JNK) by Activated Hepatocyte Fibroblast Growth Factor Receptor 4 (FGFR4) and Bile Acids J. Biol. Chem., May 6, 2005; 280(18): 17707 - 17714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Steiling, M. Muhlbauer, F. Bataille, J. Scholmerich, S. Werner, and C. Hellerbrand Activated Hepatic Stellate Cells Express Keratinocyte Growth Factor in Chronic Liver Disease Am. J. Pathol., October 1, 2004; 165(4): 1233 - 1241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Yu, F. Wang, C. Jin, X. Huang, D. L. Miller, C. Basilico, and W. L. McKeehan Role of Fibroblast Growth Factor Type 1 and 2 in Carbon Tetrachloride-Induced Hepatic Injury and Fibrogenesis Am. J. Pathol., October 1, 2003; 163(4): 1653 - 1662. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
