Tissue inhibitor of metalloproteinases-2 (TIMP-2) in rat liver cells is increased by lipopolysaccharide and prostaglandin E2.
To explore the functional role of TIMP-2 in liver, we determined TIMP-2 mRNA levels in primary rat hepatocytes and in total rat liver. Rat hepatocytes constitutively express TIMP-2 mRNA at a low level. Incubation with dexamethasone, prostaglandin E2 and a combination of inflammatory cytokines leads to an up-regulation of TIMP-2 mRNA. In rats in vivo we found a dramatic increase of TIMP-2 expression after intraperitoneal injection of lipopolysaccharide. Compared to our previous findings on TIMP-1 we conclude that TIMP-2 mRNA expression is regulated in a distinct and partially opposite manner. Over-production of TIMP-2 could inhibit the activity of metalloproteinases and thus lead to matrix accumulation. Dysregulation of TIMP-2 synthesis might be involved in the development of liver fibrosis.
Roeb
E
E
Medizinische Klinik III, RWTH Aachen, Germany.
Rose-John
S
S
Erren
A
A
Edwards
D R
DR
Matern
S
S
Graeve
L
L
Heinrich
P C
PC
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D005355:Fibrosis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D019716:Tissue Inhibitor of Metalloproteinase-2
D016207:Cytokines; D008070:Lipopolysaccharides; D011506:Proteins; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D003907:Dexamethasone; D008666:Metalloendopeptidases; D015232:Dinoprostone