Thrombospondin induces glomerular mesangial cell adhesion and migration.
BACKGROUND
Extracellular matrix components are known to modulate mesangial cell functions as adhesion, motility and proliferation. Among other extracellular matrix components, mesangial cells have been recently described to secrete thrombospondin (TSP), a high molecular weight glycoprotein, produced by several cell types, and known to play a role in embryogenesis, wound healing, angiogenesis, and tumorigenesis. The aim of this work was the functional and molecular characterization of TSP interactions with mesangial cells.


METHODS
Adhesion of mesangial cells to TSP-coated plastic, and chemotaxis in the Boyden chamber assay were tested. In order to identify TSP active domains, heparin, known to bind to the amino-terminal region of TSP, four monoclonal antibodies directed against specific domains of the molecule, and TSP fragments obtained by enzymatic digestion were used.


RESULTS
We found that TSP induces mesangial cell adhesion and chemotaxis, in a dose dependent manner. Adhesion was inhibited by antiserum against TSP, and by an anti-CD36 monoclonal antibody tested in the presence of heparin, but not by the peptide Gly-Arg-Gly-Asp-Ser. We have also found that only the carboxy-terminal end of TSP retains the adhesive properties of the molecule, while all the fragments tested showed some degree of chemotactic activity.


CONCLUSIONS
We conclude that TSP modulates mesangial cell adhesion and motility, thus acting as a potential autocrine and paracrine regulator of mesangial cell functions in normal and pathologic conditions.
Taraboletti
G
G
Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
Morigi
M
M
Figliuzzi
M
M
Giavazzi
R
R
Zoja
C
C
Remuzzi
G
G
D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry; D019699:Thrombospondins
D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; D019699:Thrombospondins