Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High glucose inhibits mesangial cell proliferation in vitro and induces hypertrophy in mesangial cells in culture and in experimental diabetic nephropathy. Cell growth is ultimately controlled at the level of the cell cycle by cell cycle regulatory proteins. Cell cycle progression requires that cyclin-dependent kinases be activated by cyclins. Cyclin kinase inhibitors (CKI) inactivate cyclin-dependent kinases, causing cell cycle arrest. In the current study, high glucose-induced mesangial cell hypertrophy in vitro is shown to be associated with increased levels of the CKI p21, but not p27. In the streptozotocin model of experimental diabetes in the mouse, glomerular hypertrophy was associated with a selective increase in p21 expression, whereas the levels of the CKI p27 and p57 did not change. Unlike many other forms of glomerular injury, diabetic nephropathy was not associated with increased apoptosis. These results support a role for p21 in causing glomerular cell hypertrophy in diabetic nephropathy.
 ...
PMID:The cyclin kinase inhibitor p21WAF1, CIP1 is increased in experimental diabetic nephropathy: potential role in glomerular hypertrophy. 962 Dec 81

The reversibility of diabetic nephropathy remains controversial. Here, we tested whether replacing leptin could reverse the advanced diabetic nephropathy modeled by the leptin-deficient BTBR ob/ob mouse. Leptin replacement, but not inhibition of the renin-angiotensin-aldosterone system (RAAS), resulted in near-complete reversal of both structural (mesangial matrix expansion, mesangiolysis, basement membrane thickening, podocyte loss) and functional (proteinuria, accumulation of reactive oxygen species) measures of advanced diabetic nephropathy. Immunohistochemical labeling with the podocyte markers Wilms tumor 1 and p57 identified parietal epithelial cells as a possible source of regenerating podocytes. Thus, the leptin-deficient BTBR ob/ob mouse provides a model of advanced but reversible diabetic nephropathy for further study. These results also suggest that restoration of lost podocytes is possible but is not induced by RAAS inhibition, possibly explaining the limited efficacy of RAAS inhibitors in promoting repair of diabetic nephropathy.
 ...
PMID:Reversibility of structural and functional damage in a model of advanced diabetic nephropathy. 2364 Oct 56

Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. As progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here, we identified and quantified potential glomerular progenitor cells that could be a source for restored podocytes. DN was identified in 31 human renal biopsy cases and separated into morphologically early or advanced lesions. Markers of podocytes (WT-1, p57), parietal epithelial cells (PECs) (claudin-1), and cell proliferation (Ki-67) were identified by immunohistochemistry. Podocyte density was progressively reduced with DN. Cells marking as podocytes (p57) were present infrequently on Bowman's capsule in controls, but significantly increased in histologically early DN. Ki-67-expressing cells were identified on the glomerular tuft and Bowman's capsule in DN, but rarely in controls. Cells marking as PECs were present on the glomerular tuft, particularly in morphologically advanced DN. These findings show evidence of phenotypic plasticity in podocyte and PEC populations and are consistent with studies in the BTBR ob/ob murine model in which reversibility of DN occurs with podocytes potentially regenerating from PEC precursors. Thus, our findings support, but do not prove, that podocytes may regenerate from PEC progenitors in human DN. If so, progression of DN may represent a modifiable net balance between podocyte loss and regeneration.
...
PMID:The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy. 2637 29