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-beta1) upregulation. TGF-beta1 enhances epithelial-to-mesenchymal transdifferentiation. Albuminuria also enhances the expression of macrophage chemotactic protein-1 and macrophage inflammatory protein-1alpha, thus leading to increased interstitial inflammation. TGF-beta1 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 epithelial tubular cells and stimulates the growth of epithelial cells (mitogen), enhances the motility of epithelial cells (motogen), induces renal epithelial tubule regeneration (morphogen) and enhances angiogenesis (angiogen). The balance between TGF-beta1 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.
Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy. gf.ferraccioli@rm.unicatt.it
G
G
Ferraccioli
G
G
Romano
D017209:Apoptosis / Q000502:physiology; D018450:Disease Progression; D004727:Endothelium / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007511:Ischemia / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000473:pathology / Q000503:physiopathology*; D011507:Proteinuria / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000276:immunology
D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor