PMID- 19736547
OWN - NLM
STAT- MEDLINE
DCOM- 20091112
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 89
IP  - 11
DP  - 2009 Nov
TI  - Curcumin eliminates oxidized LDL roles in activating hepatic stellate cells by 
      suppressing gene expression of lectin-like oxidized LDL receptor-1.
PG  - 1275-90
LID - 10.1038/labinvest.2009.93 [doi]
AB  - Type II diabetes mellitus (T2DM) is often accompanied by non-alcoholic 
      steatohepatitis (NASH) and associated with hypercholesterolemia, that is, 
      increased levels of plasma low-density lipoprotein (LDL) and oxidized LDL 
      (ox-LDL). Approximately one-third of NASH develops hepatic fibrosis. The role of 
      hypercholesterolemia in T2DM and NASH-associated hepatic fibrogenesis remains 
      obscure. We previously reported that the phytochemical curcumin inhibited the 
      activation of hepatic stellate cells (HSCs), the major effector cells during 
      hepatic fibrogenesis, and protected the liver from fibrogenesis in vitro and in 
      vivo. The aims of this study are to evaluate the role of ox-LDL in activation of 
      HSCs, to assess curcumin effects on eliminating the role of ox-LDL, and to 
      further explore the underlying mechanisms. In this report, we observe that ox-LDL 
      alters the expression of genes closely relevant to HSC activation, which is 
      eliminated by curcumin. Curcumin suppresses gene expression of lectin-like 
      oxidized LDL receptor-1 (LOX-1), leading to the blockade of the transport of 
      extracellular ox-LDL into cells. This suppressive effect of curcumin results from 
      the interruption of Wnt signaling and the activation of peroxisome 
      proliferator-activated receptor-gamma (PPARgamma). In conclusion, these results 
      support our initial hypothesis and demonstrate that ox-LDL stimulates HSC 
      activation, which is eliminated by curcumin by suppressing lox-1 expression by 
      interrupting Wnt signaling and stimulating PPARgamma activity. These results 
      provide novel insights into the role of ox-LDL in T2DM and NASH-associated 
      hepatic fibrogenesis and mechanisms by which curcumin suppresses ox-LDL-induced 
      HSC activation, as well as the implication of curcumin in the treatment of T2DM 
      and NASH-associated hepatic fibrosis.
FAU - Kang, Qiaohua
AU  - Kang Q
AD  - Department of Pathology, School of Medicine, Saint Louis University, St Louis, MO 
      63104, USA.
FAU - Chen, Anping
AU  - Chen A
LA  - eng
GR  - R01 DK047995/DK/NIDDK NIH HHS/United States
GR  - R01 DK047995-14/DK/NIDDK NIH HHS/United States
GR  - R01 DK 047995/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090907
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Coloring Agents)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (PPAR gamma)
RN  - 0 (Receptors, Oxidized LDL)
RN  - 0 (oxidized low density lipoprotein)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
CIN - Lab Invest. 2009 Nov;89(11):1190-1. PMID: 19861966
MH  - Animals
MH  - Blotting, Western
MH  - Coloring Agents/*pharmacology
MH  - Curcumin/*pharmacology
MH  - Diabetes Mellitus, Type 2/complications/metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Gene Silencing
MH  - Hepatic Stellate Cells/*drug effects/metabolism
MH  - Hypercholesterolemia/complications/metabolism
MH  - Lipoproteins, LDL/genetics/*metabolism
MH  - Liver Cirrhosis/complications/metabolism
MH  - Male
MH  - Mutagenesis, Site-Directed
MH  - PPAR gamma/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Oxidized LDL/*genetics
PMC - PMC2783367
MID - NIHMS133979
COIS- Disclosures Section: The authors have nothing to disclose.
EDAT- 2009/09/09 06:00
MHDA- 2009/11/13 06:00
PMCR- 2010/05/01
CRDT- 2009/09/09 06:00
PHST- 2009/09/09 06:00 [entrez]
PHST- 2009/09/09 06:00 [pubmed]
PHST- 2009/11/13 06:00 [medline]
PHST- 2010/05/01 00:00 [pmc-release]
AID - S0023-6837(22)02945-2 [pii]
AID - 10.1038/labinvest.2009.93 [doi]
PST - ppublish
SO  - Lab Invest. 2009 Nov;89(11):1275-90. doi: 10.1038/labinvest.2009.93. Epub 2009 
      Sep 7.