Matrix Metalloproteases from Chondrocytes Generate an Antiangiogenic 16 Kda Prolactin.
From: Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, México.
Journal of cell science
- Publish Date: May 2006
- ISSN: 0021-9533
- Volume: 119
- Issue: Pt 9
- Pages: 1790-800
- Medium: Print
- Language: English
- Citation (JAMA): Macotela Yazmín, Aguilar Manuel B, Guzmán-Morales Jessica, et al. Matrix Metalloproteases from Chondrocytes Generate an Antiangiogenic 16 Kda Prolactin.. J. Cell. Sci. May 2006;119:1790-800
Abstract
The 16 kDa N-terminal fragment of prolactin (16K-prolactin) is a potent antiangiogenic factor. Here, we demonstrate that matrix metalloproteases (MMPs) produced and secreted by chondrocytes generate biologically functional 16K-prolactin from full-length prolactin. When incubated with human prolactin at neutral pH, chondrocyte extracts and conditioned medium, as well as chondrocytes in culture, cleaved the Ser155-Leu156 peptide bond in prolactin, yielding - upon reduction of intramolecular disulfide bonds - a 16 kDa N-terminal fragment. This 16K-prolactin inhibited basic fibroblast growth factor (FGF)-induced endothelial cell proliferation in vitro. The Ser155-Leu156 site is highly conserved, and both human and rat prolactin were cleaved at this site by chondrocytes from either species. Conversion of prolactin to 16K-prolactin by chondrocyte lysates was completely abolished by the MMP inhibitors EDTA, GM6001 or 1,10-phenanthroline. Purified MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-13 cleaved human prolactin at Gln157, one residue downstream from the chondrocyte protease cleavage site, with the following relative potency: MMP-8 > MMP-13 > MMP-3 > MMP-1= MMP-2 > MMP-9. Finally, chondrocytes expressed prolactin mRNA (as revealed by RT-PCR) and they contained and released antiangiogenic N-terminal 16 kDa prolactin (detected by western blot and endothelial cell proliferation). These results suggest that several matrix metalloproteases in cartilage generate antiangiogenic 16K-prolactin from systemically derived or locally produced prolactin.
Mesh Headings (Keywords): Amino Acid Sequence, Angiogenesis Inhibitors, Animals, Cells, Cultured, Chondrocytes, Culture Media, Conditioned, Humans, Male, Matrix Metalloproteinases, Molecular Sequence Data, Molecular Weight, Peptide Fragments, Prolactin, RNA, Messenger, Rats, Rats, Wistar
Check for Full Text / PubMed Unique Identifier (PMID): 16608881
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