title: Effects of anti-alpha1 integrin subunit antibody on anti-Thy-1 glomerulonephritis.
abstract: alpha1beta1 integrin is a potential collagen-binding extracellular matrix receptor that mediates collagen-dependent cell adhesion, proliferation, migration, and collagen matrix assembly and thereby may participate in the wound healing and pathologic scarring observed in some damaged organs. To clarify the role of alpha1beta1 integrin predominantly expressed on the mesangial cell (MC) surface in nephritic glomeruli, we investigated the involvement of MC-alpha1beta1 integrin in rat anti-Thy-1 glomerulonephritis (GN) by administering function-blocking monoclonal mouse anti-rat alpha1 integrin subunit antibody (anti-alpha1 Ab). Assay of collagen types I and IV mixed gel contraction, an in vitro model of pathologic collagen matrix remodeling, with function-blocking anti-alpha1 Ab and anti-beta1 Ab, revealed that collagen I and IV matrix reorganization is mediated by MC-alpha1beta1 integrin. In addition, conditioned medium from isolated Day 3 anti-Thy-1 nephritic glomeruli showed increased activity of MC-alpha1beta1 integrin-induced mixed collagen gel contraction as compared with that from isolated normal rat glomeruli. Treatment of Day 3 conditioned medium with anti-platelet-derived growth factor-BB antibody significantly inhibited conditioned media-induced gel contraction, whereas treatment with anti-transforming growth factor-beta antibody did not have a significant effect. Rats that received anti-alpha1 Ab from the left renal artery 3 days after anti-Thy-1 GN induction showed significant decreases of glomerular hypercellularity and mesangial matrix accumulation, including collagen I and IV in the left kidney, compared with those rats in which the left kidney received control mouse IgG1. These results suggest that MC-alpha1beta1 integrin is an important extracellular matrix receptor mediating mesangial remodeling characterized by MC proliferation and mesangial matrix reorganization in anti-Thy-1 GN. Platelet-derived growth factor-BB may be involved in early collagen matrix reorganization leading to pathologic mesangial remodeling in this GN model.
authors.affiliation: Department of Pediatrics, School of Medicine, University of Tokushima, Japan. kagami@medclin.clin.med.tokushima-u.ac.jp
authors.forename: Shoji
authors.initials: S
authors.lastname: Kagami
authors.forename: Maki
authors.initials: M
authors.lastname: Urushihara
authors.forename: Shuji
authors.initials: S
authors.lastname: Kondo
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hayashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamano
authors.forename: Klemens
authors.initials: K
authors.lastname: Löster
authors.forename: Dörte
authors.initials: D
authors.lastname: Vossmeyer
authors.forename: Werner
authors.initials: W
authors.lastname: Reutter
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003094:Collagen / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D005920:Glomerular Mesangium / Q000378:metabolism; D005921:Glomerulonephritis / Q000209:etiology* / Q000628:therapy; D039222:Integrin alpha1beta1; D016023:Integrins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018800:Thy-1 Antigens / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D014945:Wound Healing
chemical_list: D000911:Antibodies, Monoclonal; D039222:Integrin alpha1beta1; D016023:Integrins; D010982:Platelet-Derived Growth Factor; D018800:Thy-1 Antigens; D016212:Transforming Growth Factor beta; C095477:platelet-derived growth factor AB; D003094:Collagen