Expression of Ras GTPases in normal kidney and in glomerulonephritis.
BACKGROUND
Small monomeric Ras GTPases play critical and specific roles in the control of cellular proliferation and apoptosis but the expression of the three Ras isoforms (Ha-Ras, Ki-Ras and N-Ras) in human renal tissue is unknown. This work is an immunohistochemical study of Ras expression in normal renal tissue and in membranous glomerulonephritis (MGN), IgA nephropathy (IgAN) and IgA-negative mesangioproliferative glomerulonephritis (MPGN).


METHODS
Formalin-fixed, paraffin-embedded tissue was stained using pan-Ras monoclonal antibody (mAb) and Ras isoform-specific mAb. Detection employed a (DAKO Envision) modified polymer system.


RESULTS
The expression of Ras isoforms in normal human kidney was cell-specific. For example, N-Ras was detected in tubule epithelial cells but not in glomerular or interstitial cells. Ki-Ras was expressed in mesangial cells, interstitial cells and in proximal convoluted tubule cells (PCT) (particularly localized at brush borders) and in collecting duct cells (CD) (localized to cell membranes) but not in podocytes. Cytoplasmic Ha-Ras was detected in all the above cell types except podocytes. MGN was associated with podocyte expression of all three Ras isoforms and with reduced mesangial cell expression of Ha-Ras and Ki-Ras. IgAN was characterized by podocyte expression of Ha-Ras (but not Ki-Ras) and reduced mesangial cell expression of Ki-Ras without alterations in mesangial Ha-Ras expression. MPGN was associated with reduced mesangial cell Ha-Ras and Ki-Ras expression without significant podocyte Ras expression.


CONCLUSIONS
These disease-specific and isoform-specific alterations in Ras expression may be of significance in pathogenesis and warrant further functional investigation.
Kocher
Hemant M
HM
Department of Surgery, King's College Hospital, Guy's King's and St Thomas' School of Medicine, King's College London, London, UK.
Moorhead
Jane
J
Sharpe
Claire C
CC
Dockrell
Mark E C
ME
Al-Nawab
Mashal
M
Hendry
Bruce M
BM
D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D011905:Genes, ras / Q000502:physiology; D005920:Glomerular Mesangium / Q000378:metabolism* / Q000473:pathology; D005921:Glomerulonephritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012016:Reference Values
D020033:Protein Isoforms; D020559:Monomeric GTP-Binding Proteins