Abstract
Collapsing glomerulopathy is a relatively new and debated podocytopathy. Among several conjectures, inflammatory injury orchestrated by podocytes is emerging to explain the pathogenesis of collapsing glomerulopathy. Here, we briefly summarize recent studies in support of this novel and intriguing hypothesis.
Immunohistochemical analyses of markers conventionally used to demarcate podocytes apart from parietal epithelium identified the parietal podocyte. MafB-deficient mice exhibited abnormal podocyte and macrophage differentiation, suggesting ancestral and functional overlap. These apparent developmental anomalies were detected in studies showing an admixture of hyperplastic podocytes with macrophage epitopes and hyperplastic parietal epithelium in pseudocrescents and in true crescents. Experimental antibody-mediated injury of podocytes could trigger capillary collapse and pseudocrescent formation marked by recruitment of epithelial cells from Bowman's capsule. In contrast, experimental stabilization of hypoxia-inducible factors within podocytes--a known inflammatory response by macrophages--could trigger podocyte proliferation and the formation of true necrotizing crescents.
Preliminary evidence suggests that visceral and parietal podocytes may become macrophage-like inflammatory mediators of proliferative epithelial injury within the glomerulus. This may manifest as collapsing glomerulopathy or crescentic glomerulonephritis--lesions that appear to be anatomically and pathogenically linked.
