Molecular characterization and functional analysis of porcine macrophage migration inhibitory factor (MIF) gene.
Originally identified as a cytokine that inhibits the migration of macrophages from capillaries, MIF has now emerged to be a multifunctional factor involved in immune response, glucose and lipid metabolism. We report here the molecular characterization of porcine MIF gene, which resides on chromosome 14q21.3 and encodes 114 amino acids. Porcine MIF mRNA was found to be highly expressed in stomach, to a lesser extent in spleen, and at the lowest levels in skeletal muscle and heart. To gain further insight into the functional regulation of MIF, we cloned the porcine MIF promoter and verified its functionality using luciferase reporter assay. In NIH 3T3 cells, the endogenous MIF mRNA level was up-regulated by rosiglitazone treatment in a dose-dependent manner, which was accompanied by a concurrent increase in peroxisome proliferator-activated receptor (PPAR)gamma2 transcription. Over-expression of porcine PPARgamma2 in NIH 3T3 cells could also up-regulate the transcription of MIF in the absence of rosiglitazone treatment. These observations are consistent with the bioinformatic analysis that reveals two potential PPAR binding sites within the MIF promoter. Additionally, the over-expression of resistin, a factor considered to be a link between inflammation and metabolic signals, could remarkably down-regulate the transcription of MIF in NIH 3T3 cells. Taken together, we proposed that the transcription of MIF is induced by activation of PPARgamma2 and inhibited by excessive resistin.
Chen
X D
XD
Huazhong Agricultural University, Wuhan, PR China.
Chen
Y L
YL
Wang
S B
SB
Lei
T
T
Gan
L
L
Yang
Z Q
ZQ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D033481:Chromosomes, Mammalian / Q000235:genetics; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D047495:PPAR gamma / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D021101:Radiation Hybrid Mapping; D052243:Resistin / Q000378:metabolism; D000077154:Rosiglitazone; D017422:Sequence Analysis, DNA; D034421:Sus scrofa / Q000235:genetics*; D045162:Thiazolidinediones / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D008263:Macrophage Migration-Inhibitory Factors; D047495:PPAR gamma; D052243:Resistin; D045162:Thiazolidinediones; D000077154:Rosiglitazone