Glycoportein nmb (Gpnmb) Is Upregulated with Injury in the Rat 5/6 Nephrectomy (Nx) Remnant Kidney (RK)
Y Wang, SG Adler, M Chamberlin, B Satirapoj, T Dai, J LaPage, CC Nast. Harbor-UCLA Medical Center, Torrance, CA; Cedars-Sinai Medical Center, Los Angeles, CA
Background: Gpnmb,a transmembrane glycoprotein, influences osteoblast differentiation, cell adhesion and cell migration. It is found in the renal tubulo-interstitium in an obstruction model and is increased in circulating monocytes from end stage renal disease patients. We identified markedly increased Gpnmb mRNA expression in 5/6 Nx RK using microarray with Affymetrix chip 230_2 and sought to confirm the expression and localization of Gpnmb in this model, as well as assess downstream activation of the cSrc-Syk signaling pathway, which regulates autophagy and resultant tubule cell survival or death.
Design: Rat 5/6 Nx RK and control kidneys (C) were stained by immunohistochemistry for Gpnmb, macrophages (F4/80), WT-1 and active phospho-Syk, and with lectins using Peanut agglutinin (PNA) and Phytogemagglutinin E (PHA-E) for tubular localization.
Results: Gpnmb staining in the cortex and medulla is detailed in the table below; there was no proximal tubular staining. At 2 and 4 wk, RK cortical distal and medullary tubules often were dilated and frequently contained Gpnmb+ cellular debris. In the 2 wk RK, phospho-Syk is upregulated in cortical distal tubular cells and occasionally co-localized with Gpnmb in the apical areas. Glomerular Gpnmb was found in capillary luminal macrophages and in areas of injury was associated with loss of WT-1 podocyte staining.
|Control||RK 2D||RK 2 Wk||RK 4Wk|
|Cortical Distal Tubular Cells||Focal apical||↑apical, mild diffuse||↑ extent, intensity||↑ extent, intensity|
|Medullary Tubular cells||Extensive, weak-moderate apical, often diffuse||No change||No change||No change|
|Glomeruli||Negative||Focal segmental capillary||Focal segmental in injured foci, capillaries||Focal segmental in injured foci, capillaries|
|Infarcted tissue||Not present||+ macrophages||+ macrophages||+ macrophages|