Expression of apoptosis-related proteins bcl-2 and bax along with transforming growth factor (TGF-beta1) in the kidney of patients with glomerulonephritides.
BACKGROUND
Apoptosis, a gene-directed form of cell death, has been involved in the resolution of renal injury but also in the development of scarring. Bcl-2 and bax are proteins related to apoptotic process that either provides a survival advantage to rapidly proliferating cells (bcl-2) or promote cell death by apoptosis (bax). Various cytokines and growth factors are involved in this process. This study investigates the expression of bcl-2 and bax and the presence of apoptotic bodies in relation to the TGF-beta1 expression at the time of diagnosis in the renal biopsies of patients with glomerulonephritis (GN).


METHODS
Fifty patients with various types of GN and ten controls were included in the study. Bcl-2, bax and Transforming Growth Factor (TGF-beta1) positive cells were detected in kidney biopsies by immunohistochemistry, while apoptotic cells were detected by in situ end labeling of fragmented DNA (ISEL). Morphometric analysis was used for quantitation of immunostaining.


RESULTS
The intensity of bcl-2, bax and TGF-beta1 immunostaining in the renal tissue of patients with GN was significantly more to the observed in the control biopsies. Bcl-2 and bax were expressed within the epithelial cells of proximal, distal and collecting tubules and in the renal interstitium. Bax and bcl-2 proteins were also identified within the glomeruli in a few patients but their distribution was not related to the type of GN. TGF-beta1 was expressed in the cytoplasm of tubular epithelial cells and to a lesser extent in the renal interstitium and glomeruli. A positive correlation of TGF-beta1 with the extent of bax immunostaining (r=0.498, p<0.05) and an inverse correlation with that of bcl-2 (r= -0.490, p<0.05) were identified. Apoptotic bodies were identified only in the renal tissue of patients with GN and were mainly localized among tubular epithelial and interstitial cells.


CONCLUSIONS
The intensity of bcl-2 and bax proteins expression and the presence of apoptotic bodies in the renal tissue of patients with GN suggest that apoptotic process is ongoing during the evolution of renal disease. The correlation of TGF-beta1 expression with that of apoptosis-related proteins might represent an implication of this growth factor with apoptotic process in the human diseased kidney.
Goumenos
Dimitrios S
DS
Department of Internal Medicine-Nephrology, University Hospital of Patras, Patras, Greece. dgoumenos@med.upatras.gr
Tsamandas
Athanassios C
AC
Kalliakmani
Pantelitsa
P
Tsakas
Sotiris
S
Sotsiou
Florentia
F
Bonikos
Dionysis S
DS
Vlachojannis
John G
JG
D017209:Apoptosis / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein