Diabetic Tubulopathy: An Emerging Entity

摘要: In chronic glomerulopathic disease, renal function correlates more with the degree oftubulointerstitial injury than that of glomerular lesions. Proteinuria may be one pathologic links between these two intrarenal compartments. It is apparent proximal tubular epithelial cell (PTEC) assumes a proinflammatory and profibrotic role during proteinuria in which PTEC expresses variety chemokines signals culminate progressive interstitial inflammation fibrosis. During diabetes, other substrates including advanced glycation end products (AGEs), AGE intermediates, high glucose (HG) provoke even further. Glycated albumin, but not equivalent dose bovine serum albumin (BSA), stimulates IL-8 ICAM-1 expression via NF-κB-, MAPK- STAT-1-dependent pathways. Human biopsies diabetic nephropathy (DN) reveal colocalization tubules. The biologically active carbonyl intermediates methylglyoxal-BSA-AGE AGE-BSA upregulate CTGF, TGF-β, VEGF, whereas carboxymethyllysine-BSA IL-6, CCL-2, VEGF RAGE activation NF-κB signal transduction. Hyperglycemia (30 mM), mannitol, promotes (IL-6 CCL-2), (TGF-β) angiogenic (VEGF) responses cells MAPK PKC signaling induces mesenchymal transition, TGF-β1 mediated. has recently been shown toll-like receptor (TLR) implicated kidney. human DN PTEC, TLR4is upregulated plays permissive HG-induced IL-6 CCL-2 overexpression monocyte transmigration. streptozotocin-induced rat TLR2 appears to upregulated. Other novel mediators become activated exposed HG include macrophage inflammatory protein-3-α, Kruppel-like factor 6 thioredoxin-interacting protein, attenuated by peroxisome proliferator-activate dreceptor-γ activation. Collectively, phenomena suggest tubules are heavily involved pathogenesis DN. These pathophysiologic collectively described as tubulopathy.