Cytoskeletal protein expression and regenerative markers in schistosomal nephropathy.
BACKGROUND
Progression of renal diseases is related to the abnormal regulation of cellular and extracellular matrix turnover. Other factors in addition to schistosomal antigens may be relevant to the progression of schistosomal nephropathy (SN). The validity of markers of fibroblastic differentiation, alpha smooth muscle actin (alphaSMA), and vimentin, as well as the regenerative activity (PCNA/apoptosis index) in determination of progression of SN in comparison to other forms of non-schistosomal nephropathy (non-SN) is investigated.


METHODS
Three groups were included; group I pure SN (n=16), group II a diverse group of non-schistosomal patients with comparable pathologic changes on renal biopsy (n=40) and a control group (n=5). Immunohistochemical staining of myofibroblasts (alphaSMA and vimentin) and proliferating cells (PCNA) and histomorphometric analysis was done. In situ end labelling (ISEL) of DNA was used to evaluate apoptosis.


RESULTS
No differences in the patterns of distribution of positivity of the different studied markers were observed between the different nephropathy groups. Both alphaSMA and vimentin were detected in glomerular mesangial, tubular epithelial, interstitial inflammatory fibroblast-like cells and occasionally endothelial cells. PCNA and apoptotic cells were detected in tubular epithelial and interstitial cells with paucity of positive cells in the glomerulus. Significant positive correlations were detected in group I between glomerular sclerosis and interstitial markers including interstitial alphaSMA (r=0.609, P=0.001), interstitial vimentin (r=0.812, P=0.00) and interstitial apoptosis (r=0.733, P=0.001). On the other hand, glomerulosclerosis in group II showed significant positive correlations with predominantly the glomerular markers; glomerular alphaSMA (r=0.475, P=0.002), glomerular apoptosis (r=0.684, P=0.00) and glomerular PCNA (r=0.691, P=0.00). Interstitial fibrosis correlated significantly with interstitial markers in group I including interstitial alphaSMA (r=0.837, P=0.00) interstitial vimentin (r=0.929, P=0.00), interstitial apoptosis (r=0.807, P=0.00) and interstitial PCNA (r=0.617, P=0.01), while in group II it correlated with both interstitial and glomerular markers. In addition, the tubulo-interstitial ratio was significantly higher in group I in comparison with group II (P=0.024), with no difference between groups II and III.


CONCLUSIONS
Although SN may start as glomerulopathy associated with increased mesangial cellularity, the interstitial rather than the glomerular markers of myofibroblastic differentiation and those of cell turnover are playing a crucial role in late stages of schistosomal, but not in non-schistosomal nephropathies.
El-Koraie
Ahmed F
AF
University of Alexandria, Alexandria, Egypt.
Baddour
Nahid M
NM
Adam
Ahmed G
AG
El-Kashef
Essam H
EH
El Nahas
A Meguid
AM
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers; D002921:Cicatrix / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000469:parasitology* / Q000473:pathology; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012552:Schistosomiasis / Q000473:pathology / Q000503:physiopathology*; D014746:Vimentin / Q000378:metabolism
D015415:Biomarkers; D003598:Cytoskeletal Proteins; D018809:Proliferating Cell Nuclear Antigen; D014746:Vimentin