Lutheran/basal cell adhesion molecule accelerates progression of crescentic glomerulonephritis in mice

Abstract

Migration of circulating leukocytes from the vasculature into the surrounding tissue is an important component of the inflammatory response. Among the cell surface molecules identified as contributing to leukocyte extravasation is VCAM-1, expressed on activated vascular endothelium, which participates in all stages of leukocyte–endothelial interaction by binding to leukocyte surface expressed integrin VLA-4. However, not all VLA-4-mediated events can be linked to VCAM-1. A novel interaction between VLA-4 and endothelial Lutheran (Lu) blood group antigens and basal cell adhesion molecule (BCAM) proteins has been recently shown, suggesting that Lu/BCAM may have a role in leukocyte recruitments in inflamed tissues. Here, we assessed the participation of Lu/BCAM in the immunopathogenesis of crescentic glomerulonephritis. High expression of Lu/BCAM in glomeruli of mice with rapidly progressive glomerulonephritis suggests a potential role for the local expression of Lu/BCAM in nephritogenic recruitment of leukocytes. Genetic deficiency of Lu/BCAM attenuated glomerular accumulation of T cells and macrophages, crescent formation, and proteinuria, correlating with reduced fibrin and platelet deposition in glomeruli. Furthermore, we found a pro-adhesive interaction between human monocyte α4β1 integrin and Lu/BCAM proteins. Thus, Lu/BCAM may have a critical role in facilitating the accumulation of monocytes and macrophages, thereby exacerbating renal injury.

Genetic and pharmacological inhibition of microRNA-92a maintains podocyte cell cycle quiescence and limits crescentic glomerulonephritis

“…Nephrotoxic nephritis was induced in male mice (10–12 weeks of age) by intravenous injection of 15 µl of sheep anti-glomerular basement membrane (GBM) nephrotoxic serum (NTS), which was diluted with 85 µl of sterile phosphate buffer solution as previously described 65 , 66 . Serum injections were repeated twice: once on day 2 at 6 µl/g of body weight and a second time on day 3 at 7 µl/g of body weight.…”

Nuclear Factor Erythroid 2-Related Factor 2 Drives Podocyte-Specific Expression of Peroxisome Proliferator-Activated Receptor γ Essential for Resistance to Crescentic GN

“…The selective PPARg deletion in podocytes was functionally associated with increased proteinuria and a raised BUN concentration in Pod-PPARg lox mice compared with controls ( Figure 3C and D) and structurally, with a loss of an interdigitating foot process pattern ( Figure 3E). As previously described, 22 affect systemic mouse anti-sheep IgG humoral response ( Figure 4D). …”

“…Serum injections were repeated twice (on days 2 and 3) as previously reported. 22,53 Mouse Model for DXR-Induced Nephropathy…”

Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic Reticulum Stress and Attenuates Kidney Injury

“…Similar findings were observed in rat kidneys subjected to cold ischemia. ANG and BiP were also expressed during AKI associated with passive antiglomerular basement membrane (GBM) nephritis ( Figure 2, A and B) a condition associated with significant proteinuria, 24 which is known to promote ER stress. 25 Finally, BiP and ANG expression was induced in rat kidneys with acute cyclosporin nephrotoxicity (Supplemental Figure 1C).…”

“…Albuminuria was significantly increased in the animals with anti-GBM nephritis. 24 Ang knockout (Ang 2/2 ) mice. …”