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 language | English (US) |
|---|---|
| Pages (from-to) | 865-869 |
| Number of pages | 5 |
| Journal | Journal of Nephrology |
| Volume | 26 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 23 2013 |
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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 journal › Article
}
TY - JOUR
T1 - Alterations in tubular epithelial cells in diabetic nephropathy
AU - Habib, Samy L.
PY - 2013/9/23
Y1 - 2013/9/23
N2 - 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.
AB - 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.
KW - Cell matrix protein
KW - Diabetes
KW - Fibrosis
KW - Tubular injury
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U2 - 10.5301/jn.5000287
DO - 10.5301/jn.5000287
M3 - Article
VL - 26
SP - 865
EP - 869
JO - Journal of Nephrology
JF - Journal of Nephrology
SN - 1121-8428
IS - 5
ER -