Renal interstitial cells, proteinuria and progression of lupus nephritis: new frontiers for old factors

Interstitial cells, inflammatory-immune cells, tubular cells and endothelial cells of the peritubular capillaries have arisen as possible major players of the nephron damage in lupus nephritis. Increased ICAM-1, Von Willebrand factor, soluble endothelial protein C receptors and decreased ADAMS-13 point to a diffuse vascular damage. Albuminuria elicits a rapid generation of hydrogen peroxide in proximal tubular cells along with nuclear factor-kB activation, endothelin-1 and transforming growth factor (TGF-beta 1) upregulation. TGF-beta 1 enhances epithelial-to-mesenchymal transdifferentiation. Albuminuria, also enhances the expression of macrophage chemotactic protein-1 and macrophage inflammatory protein-1 alpha, thus leading to increased interstitial inflammation. TGF-beta 1 and thrombospondin-1, a putative activator of TGF-beta, induce apoptosis of peritubular capillaries, as well as of glomerular endothelial cells. All these events can be counteracted by hepatocyte growth factor (HGF), which is expressed by the epithelia] tubular cells and stimulates the growth of epithelia] cells (mitogen), enhances the motility of epithelial cells (motogen), induces renal epithelial tubule regeneration (morphogen) and enhances angiogenesis (angiogen). The balance between TGF-beta 1 and HGF could be a key to define the prognostic value of kidney histopathology at baseline and during follow-up, in lupus nephritis. Therapeutic strategies aiming at altering the biological balance in the patients are at hand to test and prove the experimental evidences.