Glomerular injury is exacerbated in diabetic integrin alpha1-null mice.
Authors Zent R, Yan X, Su Y, Hudson BG, Borza DB, Moeckel GW, Qi Z, Sado Y, Breyer MD,
Voziyan P, Pozzi A
Submitted By Matthew Breyer on 11/12/2007
Status Published
Journal Kidney international
Year 2006
Date Published 8/1/2006
Volume : Pages 70 : Not Specified
PubMed Reference 16775606
Abstract Excessive glomerular collagen IV and reactive oxygen species (ROS) production
are key factors in the development of diabetic nephropathy. Integrin
alpha1beta1, the major collagen IV receptor, dowregulates collagen IV and ROS
production, suggesting this integrin might determine the severity of diabetic
nephropathy. To test this possibility, wild-type and integrin alpha1-null mice
were rendered diabetic with streptozotocin (STZ) (100 mg/kg single
intraperitoneal injection), after which glomerular filtration rate (GFR),
glomerular collagen deposition, and glomerular basement membrane (GBM)
thickening were evaluated. In addition, ROS and collagen IV production by
mesangial cells as well as their proliferation was measured in vitro. Diabetic
alpha1-null mice developed worse renal disease than diabetic wild-type mice. A
significant increase in GFR was evident in the alpha1-null mice at 6 weeks after
the STZ injection; it started to decrease by week 24 and reached levels of
non-diabetic mice by week 36. In contrast, GFR only increased in wild-type mice
at week 12 and its elevation persisted throughout the study. Diabetic mutant
mice also showed increased glomerular deposition of collagen IV and GBM
thickening compared to diabetic wild-type mice. Primary alpha1-null mesangial
cells exposed to high glucose produced more ROS than wild-type cells, which led
to decreased proliferation and increased collagen IV synthesis, thus mimicking
the in vivo finding. In conclusion, this study suggests that lack of integrin
alpha1beta1 exacerbates the glomerular injury in a mouse model of diabetes by
modulating GFR, ROS production, cell proliferation, and collagen deposition.

Investigators with authorship
Matthew BreyerJohnson & Johnson