Effects of decidua-conditioned medium and insulin-like growth factor binding protein-1 on trophoblastic matrix metalloproteinases and their inhibitors.
The regulatory role of in vitro decidualized stromal cells (DESCM) and their main secretory product insulin-like growth factor binding protein-1 (IGFBP-1) was studied on the secretion of trophoblastic gelatinases and tissue inhibitor of metalloproteinase (TIMP-1). First trimester cytotrophoblastic cells (CTB) were obtained from abortions and cultured in vitro in presence or absence of DESCM or IGFBP-1. Secreted gelatinases were analysed in the culture supernatants by zymography and by measurements of the total gelatinolytic activity. TIMP-1, hCG, and fetal fibronectin (fFN) were measured by commercially available immunoassays. DESCM inhibited the total gelatinolytic activity of CTB but increased trophoblastic MMP-9, TIMP-1 and fFN. In contrast, IGFBP-1 increased the total gelatinolytic activity and TIMP-1, had no effect on MMP-2 , MMP-9 or fFN but inhibited hCG. It is concluded that a factor secreted by decidual cells inhibits the gelatinolytic property of trophoblast by increasing TIMP-1. Other decidual factors, as yet unidentified, increase MMP-2 and MMP-9 to an extent which does override the inhibitory effect of TIMP-1. Since in contrast to DESCM, IGFBP-1 increases the total gelatinolytic activity of CTB, it cannot be the primary active decidual factor regulating the proteolytic activity of CTB. The possibility of an integrin-mediated effect of IGFBP-1 on CTB is discussed.
Department of Obstetrics and Gynaecology, University of Geneva, Switzerland. paul.bischof@hcuge.ch
P
P
Bischof
A
A
Meisser
A
A
Campana
L
L
Tseng
D000328:Adult; D006063:Chorionic Gonadotropin / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003656:Decidua / Q000502:physiology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D011247:Pregnancy; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects* / Q000201:enzymology
D006063:Chorionic Gonadotropin; D017077:Culture Media, Conditioned; D005353:Fibronectins; D018970:Insulin-Like Growth Factor Binding Protein 1; D019715:Tissue Inhibitor of Metalloproteinase-1; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9