Fibrillin-1 regulates mesangial cell attachment, spreading, migration and proliferation.
The microfibrillar protein fibrillin-1 is present in many organs, including the vasculature, eye, and dermis, and is thought to convey structural anchorage and elastic strength. Fibrillin-1 is also a component of the mesangial matrix. To assess the functional relevance of fibrillin-1 for cell-matrix interactions in the glomerulus, we studied the attachment, spreading, migration and proliferation of mesangial cells on fibrillin-1 and the regulation of fibrillin-1 in experimental anti-Thy1.1 nephritis displaying mesangial cell migration and proliferation in vivo. During the acute phase of experimental Thy1.1 nephritis, glomerular fibrillin-1 messenger ribonucleic acid expression and protein immunoreactivity were significantly induced as compared to controls. In a hexosaminidase-based adhesion assay, mesangial cells showed concentration-dependent attachment to fibrillin-1, similar to what was observed for fibronectin. The cell attachment was Arg-Gly-Asp dependent. Further, fibrillin-1 significantly promoted spreading and focal contact formation detected by immunostaining for vinculin. Mesangial cell migration, assessed by a transmigration assay, and proliferation, measured by a 5-bromo-2'-deoxy-uridine incorporation assay, were augmented by fibrillin-1. In diabetic mice underexpressing fibrillin-1, glomerular cell proliferation, determined by counting proliferating cell nuclear antigen-positive cells in renal sections, was significantly lower than in diabetic control mice. We conclude that fibrillin-1 promotes mesangial cell attachment, spreading, migration, and proliferation. We speculate that fibrillin-1 may thus contribute to mesangial hypercellularity during glomerular disease.
Porst
M
M
Klinik für Kinder und Jugendliche, Universität Erlangen-Nürnberg, Erlangen, Germany.
Plank
C
C
Bieritz
B
B
Konik
E
E
Fees
H
H
Dötsch
J
J
Hilgers
K F
KF
Reinhardt
D P
DP
Hartner
A
A
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018450:Disease Progression; D000071838:Fibrillin-1; D000071837:Fibrillins; D005786:Gene Expression Regulation; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D008297:Male; D050527:Mesangial Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018800:Thy-1 Antigens / Q000276:immunology; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D018800:Thy-1 Antigens; C000605724:Fbn1 protein, mouse; D054392:Adipokines; C000605725:Fbn1 protein, rat