A useful model to audit liver resolution from cirrhosis in rats using functional proteomics.
BACKGROUND
We conducted a rat cirrhosis and recovery model, on the basis of which proteomics was used to audit liver resolution from cirrhosis.


METHODS
Micronodular cirrhosis was established using Sprague-Dawley rats fed thioacetamide, and spontaneous recovery from cirrhosis was acquired after thioacetamide withdrawal.


RESULTS
Over the course of a 2-, 3-, and 6-week recovery, macronodular cirrhosis, uneven liver surface, and nearly normal liver surface were acquired, respectively. Specific liver enzymes, hepatitis activity index, hepatocytes apoptosis index, number of activated Kupffer cells and hepatic stellate cells, and area of fibrosis bands consistently peaked at the end of thioacetamide administration and decreased progressively during the recovery period. mRNA expression of proinflammatory cytokines and proapoptotic molecules peaked around the end of thioacetamide administration and decreased thereafter. Using two-dimensional gel electrophoresis, the seven most upregulated and six most downregulated protein spots were analyzed by matrix-assisted laser desorption/ionization time-of-flight. Of these, GST-P2 and its isoforms, GST-alpha and GST-M, were chosen for further validation using immunohistochemistry. Expression of GST-P peaked at the 2-week recovery, whereas GST-alpha and GST-M remained at strong levels at the 6-week recovery.


CONCLUSIONS
The mechanism of resolution from cirrhosis can be extensively investigated using the presented model which, for example, showed GST isoforms performing their roles at different time phases.
Liu
Erh-Hao
EH
Department of Surgery, Chang Gung Memorial Hospital, School of Traditional Chinese Medicine, Taipei, Taiwan.
Chen
Miin-Fu
MF
Yeh
Ta-Sen
TS
Ho
Yu-Pin
YP
Wu
Ren-Chin
RC
Chen
Tse-Ching
TC
Jan
Yi-Yin
YY
Pan
Tai-Long
TL
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005982:Glutathione Transferase / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008969:Molecular Sequence Data; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013853:Thioacetamide
D016207:Cytokines; D012333:RNA, Messenger; D013853:Thioacetamide; D005982:Glutathione Transferase