PMID- 20607654
OWN - NLM
STAT- MEDLINE
DCOM- 20101005
LR  - 20211203
IS  - 1699-5848 (Electronic)
IS  - 0213-3911 (Linking)
VI  - 25
IP  - 9
DP  - 2010 Sep
TI  - A role for mammalian target of rapamycin (mTOR) pathway in non alcoholic 
      steatohepatitis related-cirrhosis.
PG  - 1123-31
LID - 10.14670/HH-25.1123 [doi]
AB  - Non-alcoholic fatty liver disease (NAFLD) encompasses the whole spectrum of 
      steatosis, non-alcoholic steatohepatitis (NASH), and NASH-related cirrhosis 
      (NASH/Cir). Although molecular advances have been made in this field, the 
      pathogenesis of NAFLD is not completely understood. The gene expression profiling 
      associated to NASH/Cir was assessed, in an attempt to better characterize the 
      pathways involved in its etiopathogenesis. METHODS: In the first step, we used 
      cDNA microarray to evaluate the gene expression profiles in normal liver (n=3) 
      and NASH/Cir samples (n=3) by GeneSifter analysis to identify differentially 
      expressed genes and biological pathways. Second, tissue microarray was used to 
      determine immunohistochemical expression of phosphorylated mTOR and 4E-BP1 in 11 
      normal liver samples, 10 NASH/Cir samples and in 37 samples of cirrhosis of other 
      etiologies to further explore the involvement of the mTOR pathway evidenced by 
      the gene expression analysis. RESULTS: 138 and 106 genes were, respectively, up 
      and down regulated in NASH/Cir in comparison to normal liver. Among the 9 
      pathways identified as significantly modulated in NASH/Cir, the participation of 
      the mTOR pathway was confirmed, since expression of cytoplasmic and membrane 
      phospho-mTOR were higher in NASH/Cir in comparison to cirrhosis of other 
      etiologies and to normal liver. CONCLUSIONS: Recent findings have suggested a 
      role for the cellular "nutrient sensor" mTOR in NAFLD and the present study 
      corroborates the participation of this pathway in NASH/Cir. Phospho-mTOR 
      evaluation might be of clinical utility as a potential marker for identification 
      of NASH/Cir in cases mistakenly considered as cryptogenic cirrhosis owing to 
      paucity of clinical data.
FAU - Kubrusly, Marcia Saldanha
AU  - Kubrusly MS
AD  - Department of Surgery, University of Sao Paulo School of Medicine, Sao Paulo, 
      Brazil. msk@usp.br
FAU - Correa-Giannella, Maria Lucia
AU  - Correa-Giannella ML
FAU - Bellodi-Privato, Marta
AU  - Bellodi-Privato M
FAU - de Sa, Sandra Valeria
AU  - de Sa SV
FAU - de Oliveira, Claudia Pinto Marques Souza
AU  - de Oliveira CP
FAU - Soares, Ibere Cauduro
AU  - Soares IC
FAU - Wakamatsu, Alda
AU  - Wakamatsu A
FAU - Alves, Venancio Avancini Ferreira
AU  - Alves VA
FAU - Giannella-Neto, Daniel
AU  - Giannella-Neto D
FAU - Bacchella, Telesforo
AU  - Bacchella T
FAU - Machado, Marcel Cerqueira Cesar
AU  - Machado MC
FAU - D'Albuquerque, Luiz Augusto Carneiro
AU  - D'Albuquerque LA
LA  - eng
PT  - Journal Article
PL  - Spain
TA  - Histol Histopathol
JT  - Histology and histopathology
JID - 8609357
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Biomarkers)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/biosynthesis/genetics
MH  - Biomarkers/analysis
MH  - Cell Cycle Proteins
MH  - Fatty Liver/genetics/*metabolism
MH  - Female
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - Humans
MH  - Immunohistochemistry
MH  - Intracellular Signaling Peptides and Proteins/genetics
MH  - Liver Cirrhosis/genetics/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phosphoproteins/biosynthesis/genetics
MH  - Protein Serine-Threonine Kinases/*biosynthesis/genetics
MH  - TOR Serine-Threonine Kinases
MH  - Tissue Array Analysis
EDAT- 2010/07/08 06:00
MHDA- 2010/10/06 06:00
CRDT- 2010/07/08 06:00
PHST- 2010/07/08 06:00 [entrez]
PHST- 2010/07/08 06:00 [pubmed]
PHST- 2010/10/06 06:00 [medline]
AID - 10.14670/HH-25.1123 [doi]
PST - ppublish
SO  - Histol Histopathol. 2010 Sep;25(9):1123-31. doi: 10.14670/HH-25.1123.