Suppressed acute phase response to LPS-induced hepatic injury in Smad3-deficient mice.
The generation of animals lacking Smad proteins has made it possible to explore the contribution of the TGF-beta-Smad signaling to immune activity in vivo. And there have been related issues actively pursued by many laboratories. Here we report that, in contrast to the markedly enhanced inflammatory response, Smad3 gene knockout (Smad3(ex8/ex8)) mice paradoxically show suppressed hepatic acute phase response to the injury induced by lipopolysaccharide (LPS) compared with wild-type mice, characterized by significantly weaker reaction of several typical acute phase proteins in mRNA level. The increase of positive acute phase proteins, e.g. alpha1-acid glycoprotein (alpha1-AGP), haptoglobin (HP) and C-reaction protein (CRP), and the decrease of negative acute phase proteins, including albumin (ALB) and transferrin (TRF), were both repressed according to the expression in liver estimated by optimized RT-PCR. Smad3(ex8/ex8) mice also exhibited lower survival rate as stimulated by LPS, which was probably on account of the suppressed acute phase response. These data are, to our knowledge, the first to implicate Smad3 in specific pathways of acute phase response in the liver.
Li
Jia-Hui
JH
Burn Institute of Chinese PLA, Department of Burn Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. lijiahui0609@hotmail.com
Lv
Kai-Yang
KY
Li
Heng-Yu
HY
Xia
Zhao-Fan
ZF
D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000150:complications* / Q000276:immunology*; D000818:Animals; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000150:complications* / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000172:deficiency* / Q000378:metabolism; D016019:Survival Analysis
D000209:Acute-Phase Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051900:Smad3 Protein; C497791:Smad3 protein, mouse