Fibrillin-1 and alpha8 integrin are co-expressed in the glomerulus and interact to convey adhesion of mesangial cells |
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Authors: | Ines Marek Gudrun Volkert Karl F Hilgers Beate Bieritz Wolfgang Rascher Dieter P Reinhardt Andrea Hartner |
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Affiliation: | 1.Department for Pediatrics and Adolescent Medicine; University Hospital of Erlangen; Erlangen, Germany;2.Department of Nephrology and Hypertension; University Hospital of Erlangen; Erlangen, Germany;3.McGill University; Department of Anatomy and Cell Biology and Faculty of Dentistry; Montreal, Canada |
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Abstract: | Fibrillin-1 is a microfibrillar extracellular matrix protein that was described to be a ligand for α8 integrin. α8 integrin is a matrix receptor specifically expressed in mesangial and smooth muscle cells of the kidney. In previous studies we detected glomerular expression of fibrillin-1. Moreover, fibrillin-1 promoted adhesion, migration, and proliferation of mesangial cells. We hypothesized that fibrillin-1 and α8 integrin might interact in the glomerulus, and thus, regulate mesangial cell properties. Our studies showed that fibrillin-1 and α8 integrin colocalize in the glomerular mesangium. Induction of experimental glomerulonephritis led to an increase of both fibrillin-1 and α8 integrin expression. In vitro studies revealed that mesangial cells deficient for α8 integrin adhere weaker to fibrillin-1 and migrate more easily on fibrillin-1 than wild-type mesangial cells. Baseline proliferation on fibrillin-1 is higher in α8 integrin-deficient mesangial cells, but the induction of proliferation is not different in α8 integrin-deficient and wild-type mesangial cells. We conclude that fibrillin-1 and α8 integrin interact, and thus, regulate mesangial cell adhesion and migration. The concomitant induction of both fibrillin-1 and α8 integrin in a self-limited model of glomerular injury points to a protective role of the interaction of fibrillin-1 with α8 integrin in the glomerulus resulting in reduced damage of the glomerular tuft as a consequence of firm adhesion of mesangial cells. |
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Keywords: | α 8 integrin-deficient mice, cell adhesion, fibrillin-1, integrins, mesangial cells, migration, glomerulus, glomerulonephritis |
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