Evidence supporting proteolytic cleavage of insulin-like growth factor binding protein-1 (IGFBP-1) protein in amniotic fluid.

Abstract

OBJECTIVE:

The purpose of this study was to determine if: 1) insulin-like growth factor binding protein-1 (IGFBP-1) in amniotic fluid (AF) exhibited proteolytic cleavage in cases of intra-amniotic inflammation; and 2) if the matrix metalloproteinases (MMP-3, MMP-8, MMP-9) in AF are associated with the degradation of IGFBP-1 in AF.

METHODS:

AF samples (n=20) were obtained from preterm gestations with and without intra-amniotic inflammation. The form of IGFBP-1 in AF was assessed by Western blot analysis and AF MMP-8 concentration was measured by ELISA. Densitometric analysis of Western blot was performed and the fragmented/intact IGFBP-1 ratio was calculated. Proteolysis of AF IGFBP-1 by MMPs was evaluated by incubating AF with exogenous human MMP-3, MMP-8 or MMP-9, and by incubating recombinant human IGFBP-1 in AF with and without inflammation.

RESULTS:

1) IGFBP-1 was present in AF without inflammation as an intact form; however, the fragmented form was dominant in AF with inflammation; 2) the ratio of fragmented/intact IGFBP-1 was significantly higher in AF with inflammation than in AF without inflammation; 3) a higher ratio of fragmented/intact IGFBP-1 was associated with a higher concentration of MMP-8; 4) in-vitro proteolysis experiments showed that AF IGFBP-1 was degraded by exogenous human MMP-3, MMP-8 and MMP-9; 5) recombinant human IGFBP-1 was fragmented in AF with inflammation, but not in AF without inflammation.

CONCLUSION:

The fragmented form of AF IGFBP-1 was significantly increased in AF with intra-amniotic inflammation, and MMPs produced in AF with intra-amniotic inflammation were associated with the proteolytic change of AF IGFBP-1.

• Authors: Si Eun Lee, Byoung-Don Han, In-Sook Park, Roberto Romero, Bo Hyun Yoon
• Journal: Journal of perinatal medicine (J Perinat Med) Vol. 36 Issue 4 Pg. 316-23 ( 2008) ISSN: 0300-5577 [Print] Germany
• PMID: 18598121 (Publication Type: Journal Article)

Chemical References

• IGFBP1 protein, human
• Insulin-Like Growth Factor Binding Protein 1
• Isoenzymes
• Matrix Metalloproteinases

Topics

• Adult
• Amniotic Fluid (enzymology, metabolism)
• Blotting, Western
• Chorioamnionitis (enzymology, metabolism)
• Female
• Humans
• Inflammation (enzymology, metabolism)
• Insulin-Like Growth Factor Binding Protein 1 (metabolism)
• Isoenzymes
• Matrix Metalloproteinases (metabolism)
• Pregnancy