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Matrix Metalloproteinase‐9 Influences Markers of Angiogenesis Following Partial Hepatectomy
Author(s) -
Deogracias Michael P,
Olle Eric W,
Ren Xiaodan,
McClintock Shan,
Warner Roscoe L,
Colletti Lisa,
Johnson Kent J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a641
Subject(s) - angiogenesis , matrix metalloproteinase , liver regeneration , vascular endothelial growth factor , extracellular matrix , hepatectomy , regeneration (biology) , hepatocyte , hepatocyte growth factor , matrix (chemical analysis) , growth factor , chemistry , biology , pathology , medicine , endocrinology , microbiology and biotechnology , biochemistry , vegf receptors , in vitro , surgery , resection , chromatography , receptor
Hepatic regeneration following partial hepatectomy is characterized by hepatocyte proliferation, extracellular matrix remodeling and angiogenesis. Matrix metalloproteinases (MMPs), particularly MMP‐9, play a role in maintenance of the extracellular matrix, as well as cellular activation and the release of cytokines and growth factors. Previous studies have shown a decrease in hepatic regeneration following partial (70%) hepatectomy in MMP‐9 deficient (MMP‐9 −/−) mice compared to wild type (MMP‐9 +/+) mice at post‐operative days 2, 3 and 5. This study examined the effect of MMP‐9 on various growth factors, including vascular endothelial growth factor (VEGF), following partial hepatectomy in mice. Protein levels of growth factors in liver tissue lysate were quantified using a Luminex™ bead‐based assay. Expression of VEGF was significantly decreased in the MMP‐9 −/− animals compared to MMP‐9 +/+ mice at day 3. As an additional measurement of endothelial cell differentiation, platelet‐endothelial cell adhesion molecule (PECAM)‐1 expression in liver tissue was ascertained using immunohistochemistry. Immunohistochemical analysis of PECAM‐1 showed significantly less staining in MMP‐9 −/− animals at day 3, followed by significantly more at day 5 when compared to MMP‐9 +/+ mice. These data suggest that MMP‐9, either directly or through matrix remodeling, is required for expression of VEGF and proper re‐vascularization during hepatic regeneration.