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.