Journal Article

The pathogenic role of the renal proximal tubular cell in diabetic nephropathy

Sydney C.W. Tang and Kar Neng Lai

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 8, pages 3049-3056
Published in print August 2012 | ISSN: 0931-0509
Published online June 2012 | e-ISSN: 1460-2385 | DOI:
The pathogenic role of the renal proximal tubular cell in diabetic nephropathy

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A growing body of evidence indicates that the renal proximal tubular epithelial cell (PTEC) plays an important role in the pathogenesis of diabetic nephropathy (DN). Microalbuminuria that intensifies over time to overt proteinuria, a hallmark of DN, is already known to activate the PTEC to induce tubulointerstitial inflammation. In addition to proteins, a number of diabetic substrates including high glucose per se, advanced glycation end-products and their carbonyl intermediates, angiotensin II, and ultrafiltered growth factors activate a number of signaling pathways including nuclear factor kappa B, protein kinase C, extracellular signal-regulated kinase 1/2, p38, signal transducer and activator of transcription-1 and the generation of reactive oxygen species, to culminate in tubular cell hypertrophy and the accumulation in the interstitium of a repertoire of chemokines, cytokines, growth factors and adhesion molecules capable of orchestrating further inflammation and fibrosis. More recently, the kallikrein-kinin system (KKS) and toll-like receptors (TLRs) in PTECs have been implicated in this process. While in vitro data suggest that the KKS contributes to the progression of DN, there are conflicting in vivo results on its precise role, which may in part be strain-dependent. On the other hand, there are both in vitro and in vivo data to suggest a role for both TLR2 and TLR4 in DN. In this review, we offer a critical appraisal of the events linking the participation of the PTEC to the pathogenesis of DN, which we believe may be collectively termed diabetic tubulopathy.

Keywords: db/db mice; diabetic nephropathy; fibrosis; inflammation; kallikrein-kinin system; proximal tubular epithelial cell; TLR4 KO mice; toll-like receptor

Journal Article.  5045 words.  Illustrated.

Subjects: Nephrology

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