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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-β1 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-β1) 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-β1 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-β1 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-β1 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. CONCLUSION: 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-β1 expression with that of apoptosis-related proteins might represent an implication of this growth factor with apoptotic process in the human diseased kidney. [ABSTRACT FROM AUTHOR]

Background. Transforming growth factor-β1 (TGF-β1), the major fibrogenic growth factor, is implicated in the pathogenesis of renal scarring in experimental and clinical nephropathies as well as in chronic allograft nephropathy. In this study we examined the pattern of changes of TGF-β1 excretion in the urine and the sites of TGF-β1 expression in the kidney of transplanted patients during the early post-transplantation period. METHODS: Eighteen renal allograft recipients were included in the study. In all patients urinary TGF-β1 levels were determined by ELISA in sequential measurements during the first two postoperative months and compared to that of 14 healthy subjects. The renal expression of TGF-β1 protein was studied in 4 patients that underwent a biopsy of the transplanted kidney at the same period. All patients were treated with prednisolone, cyclosporin, and mycophenolate mofetil. RESULTS: Urinary TGF-β1 levels were increased during the first postoperative days. Although they were gradually reduced during the first two post-operative months, they remained significantly higher compared to those of normal subjects (580 ± 148 ng/24 h vs. 310 ± 140 ng/24 h p<0.01). The decline of urinary TGF-β1 excretion followed that of serum creatinine. TGF-β1 protein expression was identified within the cytoplasm of tubular epithelial cells of transplanted patients. CONCLUSIONS: Elevated urinary TGF-β1 levels are observed during the early post-transplantation period in renal allograft recipients and are maintained high even after restoration of renal function to normal. [ABSTRACT FROM AUTHOR]

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., Conclusion: 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.