| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pediatrics, The Feinberg School of Medicine, Northwestern University, The Lakeside VA Medical Center, and the Children's Memorial Institute for Education and Research, Chicago, IL, USA
2 Department of Pathology, The Feinberg School of Medicine, Northwestern University, The Lakeside VA Medical Center, and the Children's Memorial Institute for Education and Research, Chicago, IL, USA
3 Department of Medicine, The Feinberg School of Medicine, Northwestern University, The Lakeside VA Medical Center, and the Children's Memorial Institute for Education and Research, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: a-sahai{at}northwestern.edu.
The pathogenesis of nonalcoholic steatohepatitis (NASH) is poorly defined. Feeding mice a diet
deficient in methionine and choline (MCD diet) induces experimental NASH. Osteopontin
(OPN) is a Th1 cytokine that plays an important role in several fibroinflammatory diseases. We
examined the role of OPN in the development of experimental NASH. A/J mice were fed MCD
or control diet for up to 12 weeks, and serum ALT, liver histology, oxidative stress, and the
expressions of OPN, TNF
, and collagen I were assessed at various time points. MCD diet-fed
mice developed hepatic steatosis starting at 1 week and inflammation by 2 weeks; serum ALT
increased from day 3. Hepatic collagen I mRNA expression increased during 1-4 weeks, and
fibrosis appeared at 8 weeks. OPN protein expression was markedly increased on day 1 of MCD
diet and persisted up to 8 weeks, whereas OPN mRNA expression was increased at week 4.
TNF expression was increased from day 3 to 2 weeks, and evidence of oxidative stress did not
appear until 8 weeks. Increased expression of OPN was predominantly localized in hepatocytes.
Hepatocytes in culture also produced OPN which was stimulated by TGF
and TNF. Moreover,
MCD diet-induced increases in serum ALT levels, hepatic inflammation and fibrosis were
markedly reduced in OPN-/- mice when compared with OPN+/+ mice. In conclusions, our results
demonstrate an upregulation of OPN expression early in the development of steatohepatitis and
suggests an important role for OPN in signaling the onset of liver injury and fibrosis in
experimental NASH.
This article has been cited by other articles:
|
|
 |
|
  A. Banerjee, R. Rose, G. A. Johnson, R. C. Burghardt, and S. K. Ramaiah The Influence of Estrogen on Hepatobiliary Osteopontin (SPP1) Expression in a Female Rodent Model of Alcoholic Steatohepatitis Toxicol Pathol, June 1, 2009; 37(4): 492 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bertola, V. Deveaux, S. Bonnafous, D. Rousseau, R. Anty, A. Wakkach, M. Dahman, J. Tordjman, K. Clement, S. E. McQuaid, et al. Elevated Expression of Osteopontin May Be Related to Adipose Tissue Macrophage Accumulation and Liver Steatosis in Morbid Obesity Diabetes, January 1, 2009; 58(1): 125 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Lee, A. Banerjee, Y. Ueno, and S. K. Ramaiah Potential Relationship between Hepatobiliary Osteopontin and Peroxisome Proliferator-Activated Receptor {alpha} Expression following Ethanol-Associated Hepatic Injury In Vivo and In Vitro Toxicol. Sci., November 1, 2008; 106(1): 290 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Rinella, M. S. Elias, R. R. Smolak, T. Fu, J. Borensztajn, and R. M. Green Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet J. Lipid Res., May 1, 2008; 49(5): 1068 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Ramaiah and S. Rittling Pathophysiological Role of Osteopontin in Hepatic Inflammation, Toxicity, and Cancer Toxicol. Sci., May 1, 2008; 103(1): 4 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Ramaiah and H. Jaeschke Role of Neutrophils in the Pathogenesis of Acute Inflammatory Liver Injury Toxicol Pathol, October 1, 2007; 35(6): 757 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Lee, J. S. Yan, R. K. Ng, S. Kakar, and J. J. Maher Polyunsaturated fat in the methionine-choline-deficient diet influences hepatic inflammation but not hepatocellular injury J. Lipid Res., August 1, 2007; 48(8): 1885 - 1896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sahai, X. Pan, R. Paul, P. Malladi, R. Kohli, and P. F. Whitington Roles of phosphatidylinositol 3-kinase and osteopontin in steatosis and aminotransferase release by hepatocytes treated with methionine-choline-deficient medium Am J Physiol Gastrointest Liver Physiol, July 1, 2006; 291(1): G55 - G62. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Banerjee, R. C. Burghardt, G. A. Johnson, F. J. White, and S. K. Ramaiah The Temporal Expression of Osteopontin (SPP-1) in the Rodent Model of Alcoholic Steatohepatitis: A Potential Biomarker Toxicol Pathol, June 1, 2006; 34(4): 373 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Sundaram, P. F. Whitington, and R. M. Green Steatohepatitis develops rapidly in transgenic mice overexpressing Abcb11 and fed a methionine-choline-deficient diet Am J Physiol Gastrointest Liver Physiol, June 1, 2005; 288(6): G1321 - G1327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sahai, P. Malladi, X. Pan, R. Paul, H. Melin-Aldana, R. M. Green, and P. F. Whitington Obese and diabetic db/db mice develop marked liver fibrosis in a model of nonalcoholic steatohepatitis: role of short-form leptin receptors and osteopontin Am J Physiol Gastrointest Liver Physiol, November 1, 2004; 287(5): G1035 - G1043. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
