title: Fibrillin-1 and alpha8 integrin are co-expressed in the glomerulus and interact to convey adhesion of mesangial cells.
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.
authors.affiliation: a Department for Pediatrics and Adolescent Medicine ; University Hospital of Erlangen ; Erlangen , Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Marek
authors.forename: Gudrun
authors.initials: G
authors.lastname: Volkert
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hilgers
authors.forename: Beate
authors.initials: B
authors.lastname: Bieritz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rascher
authors.forename: Dieter P
authors.initials: DP
authors.lastname: Reinhardt
authors.forename: Andrea
authors.initials: A
authors.lastname: Hartner
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D000071838:Fibrillin-1; D000071837:Fibrillins; D005921:Glomerulonephritis / Q000378:metabolism; D039001:Integrin alpha Chains / Q000235:genetics*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054392:Adipokines
chemical_list: D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071837:Fibrillins; D039001:Integrin alpha Chains; D008840:Microfilament Proteins; C000605724:Fbn1 protein, mouse; D054392:Adipokines; C000605725:Fbn1 protein, rat; C093856:integrin alpha8
keywords: BSA, bovine serum albumin; FCS, fetal calf serum; FN, fibronectin; cell adhesion; fibrillin-1; glomerulonephritis; glomerulus; integrins; mesangial cells; migration; sd, standard deviation; wt, wild-type.; α8 integrin-deficient mice; α8−/−, alpha8 integrin-deficient