Effects of SIRPalpha1 on liver regeneration after partial hepatectomy in rat.
BACKGROUND
SIRPalpha1 is well known as a negative regulator for cell proliferation through the regulation of the activity of receptor tyrosine kinase with ITAM motif. No investigation to data was undertaken on SIRPalpha1 involving liver regeneration.


METHODS
Adult male Sprague-Dawley rats underwent approximately 70% partial hepatectomy (PH) or sham operation (SO). Liver specimens were collected at 2, 6, 12, 24, 30, 48, 72, 120, 168, and 240 h after PH or SO. SIRPalpha1 expression was determined in mRNA level by Northern blotting as well as in protein levels via immunohistochemical staining.


RESULTS
SO treatment did not induce remarkable changes in SIRPalpha1 expression; however, the level of a 3.9-kb transcript for SIRPalpha1 was significantly up-regulated after PH (versus SO, P < 0.05). SIRPalpha1 mRNA expression in the regenerating liver displayed a biphasic response with its first large peak at as early as 12h followed by a second phase of up-regulation from 48 to 120 h post-PH. SIRPalpha1 mRNA expression returned to its physiological level 168 h later. As seen from immunohistochemistry experiments, SIRPalpha1 protein mainly located in membrane was expressed uniquely in regenerating hepatocytes. Similarly, PH-induced overexpression for SIRPalpha1 protein occurred between 12 and 168 h with a peak level at 24h after surgery.


CONCLUSIONS
SIRPalpha1, a principle negative regulator for cell proliferation, may also play a role in the termination of hepatic proliferation during liver regeneration induced by physiological stress or pathological states, such as PH, drugs, toxins, etc.
Qin
Jian-Min
JM
International Co-operational Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, 225 Changhai Road, Shanghai 200438, People's Republic of China.
Li
Shen-Qing
SQ
Liu
Shu-Qin
SQ
Zeng
Jin-Zhang
JZ
Man
Xiao-Bo
XB
Qiu
Xiu-Hua
XH
Wu
Meng-Chao
MC
Wang
Hong-Yang
HY
D000818:Animals; D000943:Antigens, Differentiation; D015152:Blotting, Northern; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D013194:Staining and Labeling; D014018:Tissue Distribution
D000943:Antigens, Differentiation; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D012333:RNA, Messenger; D011971:Receptors, Immunologic