Alterations in tubular epithelial cells in diabetic nephropathy

Samy L. Habib

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Renal hypertrophy, matrix protein accumulation and tubulointerstitial fibrosis are major pathological features of diabetic nephropathy (DN) that eventuate in renal failure. Hyperglycemia and high concentration of glucose increase matrix protein expression, but the pathogenic mechanisms are not fully understood. We have previously reported that inactivation of tuberin resulting in activation of the mammalian target of rapamycin (mTOR) pathway and increased matrix protein accumulation in cultured proximal tubular cells exposed to high glucose and in kidney cortex of rats with type 1 diabetes. In this report, we show that kidney sections of diabetic patients express higher levels of phospho-tuberin (inactive form of tuberin), and that is associated with an increase in mTOR activation as measured by phosphorylation level of p70S6K. Inactivation of tuberin and activation of mTOR lead to accumulated cell matrix proteins (fibronectin and collagen IV) mainly in tubular epithelial cells of the kidneys of diabetic patients. In addition, significant staining of vimentin as a marker of cells undergoing an epithelialto-mesenchymal transition (EMT) was detected in kidney sections of diabetic patients. On the other hand, very weak or nondetectable staining of cell matrix proteins, p-tuberin and P-p70S6K as well as vimentin was found in normal kidney sections of healthy subjects. The morphological changes in kidney sections of diabetic patients showed tubular thickening, glomerular and tubular hypertrophy, compared to normal structure of tubuli and glomeruli in kidney from healthy control subjects. These data suggest that alterations in tubular cells' structure, including tubular thickening and hypertrophy, are major mediators of the fibrotic process in DN.

Original languageEnglish (US)
Pages (from-to)865-869
Number of pages5
JournalJournal of Nephrology
Volume26
Issue number5
DOIs
StatePublished - Sep 23 2013

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Diabetic Nephropathies
Epithelial Cells
Kidney
Sirolimus
Hypertrophy
70-kDa Ribosomal Protein S6 Kinases
Vimentin
Proteins
Healthy Volunteers
Kidney Glomerulus
Staining and Labeling
Glucose
Kidney Cortex
Type 1 Diabetes Mellitus
Fibronectins
Hyperglycemia
Renal Insufficiency
Fibrosis
Collagen
Phosphorylation

Keywords

  • Cell matrix protein
  • Diabetes
  • Fibrosis
  • Tubular injury

ASJC Scopus subject areas

  • Nephrology

Cite this

Alterations in tubular epithelial cells in diabetic nephropathy. / Habib, Samy L.

In: Journal of Nephrology, Vol. 26, No. 5, 23.09.2013, p. 865-869.

Research output: Contribution to journalArticle

Habib, Samy L. / Alterations in tubular epithelial cells in diabetic nephropathy. In: Journal of Nephrology. 2013 ; Vol. 26, No. 5. pp. 865-869.
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