| Object:observe change and significance of BMP-7 and TGF-beta1 in IgA nephropathy.Method: Eighty-nine patients diagnosed as primary IgA nephropathy by renal biopsy from January 2006,1st to june 2006,30th at the second affiliated hospital of Hebei Medical University were involved in this study. All patients had been not treated with glucocorticosteroid,cytotoxic drug,ACEI and ARB.The patients with Henoch-Schonlein nephritis ,lupus nephritis,HBV-GN associated glomerulonephritis,hepatic cirrhosis glomerulopathy, psoriasis associated glomerulonephrity,thyropathy associated glomerulonephritis ,renal damage induced by rheumatoid arthritis and cancer associated nephropathy were not included in the present study. The cases complicated with acute renal tubular necrosis,acute or chronic interstitial nephritis were also excluded. According to the degree of pathological changes of IgA nephropathy under light microscope these patients were divided into three groups: group A: mild mesangioproliferative IgA nephropathy, forty seven cases; group B: moderate,severe mesangioproliferative IgA nephropathy, twenty nine cases; group C: proliferation-sclerosis and sclerosis IgA nephropathy, thirteen cases. There was comparability among three groups on sex and mean age. Blood pressure,urine protein excretion rate,serum creatinine and creatinine clearance rate were measured. Immunohistochemisty and ELISA were used to detect the level of TGF-beta1 and BMP-7 in frozen section,blood and urine; the express of TGF-beta1mRNA and BMP-7mRNA in paraffin section were observed by situ hybridization.The number of sclerosing glomeroruli ,crescent and the area of renal interstitial fibrosis on paraffin section were calculated under light microscope. The positive area of TGF-beta1/BMP-7 protein and mRNA in renal tissue were measured using computer image analyses system. The values given in this paper are presented as X±S. The differences between groups were performed using ANOVA and correlation were calculated using Spearman rank correlation, all statistical tests were performed using solftware Stata 8.0.Result: In all cases of IgA nephropathy, renal tissue showed abundant expression of BMP-7 in tubular epithelial cytoplasm of renal cortex and medulla , and negligible expression in glomeruli. With the progress of pathological change in IgA nephropathy, the number of renal tubule was decreased, positive area of BMP-7 in renal tissue was also decreased (P<0.01). The positive expression TGF-beta1 was observed mainly in the cavosurface cytoplasm of tubular epithelial cells of renal cortex and medulla, but a little in glomeruli. In group A, TGF-beta1 had a certain expression; in group B, its expression was significantly increased; in group C, its expression was obviously decreased; there was a significant difference in three groups (P<0.01).The positive area of BMP-7 in renal tissue was positively correlated with the level of BMP-7 in blood (r=0.803, P<0.01) and urine (r=0.795, P<0.01), the positive area of BMP-7mRNA in renal tissue (r=0.898, P<0.01) and Ccr (r=0.840, P<0.01); negatively correlated with systolic blood pressure (r=-0.783, P<0.01), diastolic blood pressure (r=-0.770, P<0.01), urine protein excretion rate (r=-0.788, P<0.01), the number of sclerosing glomeruli (r=-0.836, P<0.01), the number of crescent (r=-0.790, P<0.01) and the area of renal interstitial fibrosis (r=-0.772, P<0.01). No correlation was observed between the positive area of BMP-7 in renal tissue and the following parameters, such as the level of TGF-beta1 in blood (r=-0.043, P=0.690), the level of TGF-beta1 in urine (r=-0.037, P=0.689), the positive area of TGF-beta1 in renal tissue (r=-0.073, P=0.494) and the positive area of TGF-beta1mRNA in renal tissue (r=-0.080, P=0.791).In group A, weakly positive expression of TGF-beta1mRNA was observed in nucleus,cytoplasm of renal tubular epithelial cell and nucleus of mesangial cells.Compared with that in group A, its expression was significantly increased in group B; in group C, its expression was obviously decreased; there was a significant difference in three groups (P<0.01).The positive area of TGF-beta1mRNA in renal tissue had positive correlation with the positive area of TGF-beta1 (r=0.901, P<0.01), the level of TGF-beta1 in blood (r=0.880, P<0.01), the level of TGF-beta1 in urine (r=0.891, P<0.01) and urine protein excretion rate (r=0.293, P=0.035); no correlation was found with the level of BMP-7 in blood (r=-0.017, P=0.641), the level of BMP-7 in urine (r=-0.080, P=0.510), the positive area of BMP-7 in renal tissue (r=-0.069, P=0.596), the positive area of BMP-7mRNA in renal tissue (r=-0.080, P=0.791), systolic blood pressure (r=0.172, P=0.146), diastolic blood pressure (r=0.163, P=0.182), Ccr (r=-0.071, P=0.498), the number of sclerosing glomeruli (r=0.035, P=0.811), the number of crescent (r=-0.088, P=0.513) and the area of renal interstitial fibrosis (r=-0.020, P=0.799).In group A, the positive expression BMP-7mRNA were observed mainly in nucleus and endochylema of renal tubular epithelial cell; In group B, its expression was significantly decreased; in group C, it was a little expression, there was a significant difference in three groups (P<0.01). The positive area of BMP-7mRNA in renal tissue had positive correlation with the level of BMP-7 in blood (r=0.894, P<0.01), the level of BMP-7 in urine (r=0.910, P<0.01) and the positive area of BMP-7 in renal tissue (r=0.898, P<0.01); negative correlation with systolic blood pressure (r=-0.796, P<0.01), diastolic blood pressure (r=-0.799, P<0.01), Scr (r=-0.853, P<0.01), urine protein excretion rate (r=-0.801, P<0.01), the number of sclerosing glomeruli (r=-0.819, P<0.01), the number of crescent (r=-0.803, P<0.01) and the area of renal interstitial fibrosis (r=-0.783, P<0.01); no correlation with the level of TGF-beta1 in blood (r=-0.017, P=0.640), the level of TGF-beta1 in urine (r=-0.023, P=0.653), the positive area of TGF-beta1 in renal tissue (r=-0.068, P=0.589) and the positive area of TGF-beta1mRNA in renal tissue (r=-0.080, P=0.791).Among three groups, the level of TGF-beta1 in blood and urine increased significantly with the degree of glomerular proliferation (P<0.01),but decreased obviously with the appearance and progression of glomerular sclerosis, tubular atrophy and renal interstitial fibrosis (P<0.01). The level of BMP-7 in blood and urine decreased gradually with the progression of glomerular, tubular atrophy and renal interstitial pathological changes (P<0.01). The level of BMP-7 in blood had positive correlation with the level of BMP-7 in urine (r=0.802, P<0.01), the positive area of BMP-7 in renal tissue (r=0.803, P<0.01), the positive area of BMP-7mRNA in renal tissue (r=0.894, P<0.01) and Ccr (r=0.840, P<0.01); negative correlation with systolic blood pressure (r=-0.808, P<0.01), diastolic blood pressure (r=-0.783, P<0.01), urine protein excretion rate (r=-0.726, P<0.01), the number of sclerosing glomeruli (r=-0.830, P<0.01), the number of crescent (r=-0.827, P<0.01) and the area of renal interstitial fibrosis (r=-0.815, P<0.01); no correlation with the level of TGF-beta1 in blood (r=-0.043, P=0.690), the level of TGF-beta1 in urine (r=-0.018, P=0.582), the positive area of TGF-beta1 in renal tissue (r=-0.021, P=0.489) and the positive area of TGF-beta1mRNA in renal tissue (r=-0.017, P=0.640).The level of BMP-7 in urine had positive correlation with the level of BMP-7 in blood (r=0.802, P<0.01), the positive area of BMP-7 in renal tissue (r=0.795, P<0.01), the positive area of BMP-7mRNA in renal tissue (r=0.910, P<0.01) and Ccr (r=0.840, P<0.01); negative correlation with systolic blood pressure (r=-0.778, P<0.01), diastolic blood pressure (r=-0.767, P<0.01), urine protein excretion rate (r=-0.752, P<0.01), the number of sclerosing glomeruli (r=-0.818, P<0.01), the number of crescent (r=-0.834, P<0.01), and the area of renal interstitial fibrosis (r=-0.776, P<0.01); no correlation with the level of TGF-beta1 in blood (r=-0.043, P=0.690), the level of TGF-beta1 in urine (r=-0.082, P=0.446), the positive area of TGF-beta1 in renal tissue (r=-0.073, P=0.494) and the positive area of TGF-beta1mRNA in renal tissue (r=-0.080, P=0.510).The level of TGF-beta1 in blood had positive correlation with the level of TGF-beta1 in urine (r=0.792, P<0.01), the positive area of TGF-beta1 in renal tissue (r=0.823, P<0.01), the positive area of TGF-beta1mRNA in renal tissue (r=0.880, P<0.01) and urine protein excretion rate (r=0.307, P<0.01); no correlation with systolic blood pressure (r=0.202, P=0.058), diastolic blood pressure (r=0.161, P=0.132), Ccr (r=-0.068, P=0.526), the number of sclerosing glomeruli (r=0.047, P=0.661), the number of crescent (r=0.011, P=0.540), the area of renal interstitial fibrosis (r=0.011, P=0.915), the level of BMP-7 in blood (r=-0.043, P=0.690), the level of BMP-7 in urine (r=-0.018, P=0.582), the positive area of BMP-7 in renal tissue (r=-0.043, P=0.690) and the positive area of BMP-7mRNA in renal tissue (r=-0.017, P=0.640).The level of TGF-beta1 in urine had positive correlation with the level of TGF-beta1 in blood, the positive area of TGF-beta1 in renal tissue (r=0.801, P<0.01), the positive area of TGF-beta1mRNA in renal tissue (r=0.891, P<0.01) and urine protein excretion rate (r=0.237, P=0.026); no correlation with systolic blood pressure (r=0.130, P=0.226), diastolic blood pressure (r=0.081, P=0.450), Ccr (r=-0.031, P=0.770), the number of sclerosing glomeruli (r=0.004, P=0.968), the number of crescent (r=0.052, P=0.630), with the area of renal interstitial fibrosis (r=0.006, P=0.995), the level of BMP-7 in blood (r=-0.018, P=0.582), the level of BMP-7 in urine (r=-0.082, P=0.446), the positive area of BMP-7 in renal tissue (r=-0.037, P=0.689) and the positive area of BMP-7mRNA in renal tissue (r=-0.023, P=0.653).Systolic and diastolic blood pressure and Scr increased gradually from group A to group C ,with significant difference three groups (P<0.01); no significant difference of urine protein excretion rate was found between group B and C (P>0.05), but a significant difference was found between group B or C andA(P<0.01).Systolic blood pressure had positive correlation with diastolic blood pressure (r=0.919, P<0.01), urine protein excretion rate (r=0.765, P<0.01), the number of sclerosing glomeruli (r=0.768, P<0.01), the number of crescent (r=0.741, P<0.01) and the area of renal interstitial fibrosis (r=0.741, P<0.01); negative correlation with the level of BMP-7 in blood (r=-0.808, P<0.01), the level of BMP-7 in urine (r=-0.778, P<0.01), the positive area of BMP-7 in renal tissue (r=-0.783, P<0.01), the positive area of BMP-7mRNA in renal tissue (r=-0.796, P<0.01) and Ccr (r=-0.752, P<0.01); no correlation with the level of TGF-beta1 in blood (r=0.202, P=0.058), the level of TGF-beta1 in urine (r=0.130, P=0.226), the positive area of TGF-beta1 in renal tissue (r=0.160, P=0.135) and the positive area of TGF-beta1mRNA in renal tissue (r=0.172, P=0.146).Diastolic blood pressure had positive correlation with systolic blood pressure (r=0.919, P<0.01), urine protein excretion rate (r=0.750, P<0.01), the number of sclerosing glomeruli (r=0.787, P<0.01), the number of crescent (r=0.755, P<0.01) and the area of renal interstitial fibrosis (r=0.771, P<0.01); negative correlation with the level of BMP-7 in blood (r=-0.783, P<0.01), the level of BMP-7 in urine (r=-0.767, P<0.01), the positive area of BMP-7 in renal tissue (r=-0.770, P<0.01), the positive area of BMP-7mRNA in renal tissue (r=-0.779, P<0.01) and Ccr (r=-0.771, P<0.01); no correlation with the level of TGF-beta1 in blood (r=0.161, P=0.132), the level of TGF-beta1 in urine (r=0.081, P=0.450), the positive area of TGF-beta1 in renal tissue (r=0.146, P=0.173) and the positive area of TGF-beta1mRNA in renal tissue (r=0.163, P=0.182).Ccr had positive correlation with the level of BMP-7 in blood (r=0.848, P<0.01), the level of BMP-7 in urine (r=0.822, P<0.01), the positive area of BMP-7 in renal tissue (r=0.840, P<0.01) and the positive area of BMP-7mRNA in renal tissue (r=0.853, P<0.01); negative correlation with systolic blood pressure (r=-0.752, P<0.01), diastolic blood pressure (r=-0.771, P<0.01), urine protein excretion rate (r=-0.782, P<0.01), the number of sclerosing glomeruli (r=-0.785, P<0.01), the number of crescent (r=-0.820, P<0.01) and the area of renal interstitial fibrosis (r=-0.789, P<0.01); no correlation with the level of TGF-beta1 in blood (r=-0.068, P=0.526), the level of TGF-beta1 in urine (r=-0.031, P=0.770), the positive area of TGF-beta1 in renal tissue (r=-0.067, P=0.532) and the positive area of TGF-beta1mRNA in renal tissue (r=-0.071, P=0.489).Urine protein excretion rate had positive correlation with systolic blood pressure (r=0.765, P<0.01), diastolic blood pressure (r=0.750, P<0.01), the number of sclerosing glomeruli (r=0.735, P<0.01), the number of crescent (r=0.754, P<0.01), the area of renal interstitial fibrosis (r=0.658, P<0.01), the level of TGF-beta1 in blood (r=0.307, P=0.03), the level of TGF-beta1 in urine (r=0.237, P=0.026), the positive area of TGF-beta1 in renal tissue (r=0.226, P=0.034) and the positive area of TGF-beta1mRNA in renal tissue (r=0.293, P=0.035); negative correlation with the level of BMP-7 in blood (r=-0.726, P<0.01), the level of BMP-7 in urine (r=-0.752, P<0.01), the positive area of BMP-7 in renal tissue (r=-0.778 P<0.01) and the positive area of BMP-7mRNA in renal tissue (r=-0.801, P<0.01).With the progress of pathological change in IgA nephropathy, the number of crescent, sclerosing glomeruli and the area of renal interstitial fibrosis increased siganificantly (P<0.01).The number of sclerosing glomeruli had positive correlation with systolic blood pressure (r=0.768, P<0.01), diastolic blood pressure (r=0.787, P<0.01), urine protein excretion rate (r=0.735, P<0.01), the number of crescent (r=0.802, P<0.01) and the area of renal interstitial fibrosis (r=0.833, P<0.01); negative correlation with the level of BMP-7 in blood (r=-0.830, P<0.01), the level of BMP-7 in urine (r=-0.818, P<0.01), the positive area of BMP-7 in renal tissue (r=-0.836, P<0.01), the positive area of BMP-7mRNA in renal tissue (r=-0.819, p<0.01) and Ccr (r=-0.785, P<0.01); no correlation with the level of TGF-beta1 in blood (r=0.047, P=0.661), the level of TGF-beta1 in urine (r=0.004, P=0.968), the positive area of TGF-beta1 in renal tissue (r=0.024, P=0.822) and the positive area of TGF-beta1mRNA in renal tissue (r=0.035, P=0.811).The number of crescent had positive correlation with systolic blood pressure (r=0.741, P<0.01), diastolic blood pressure (r=0.755, P<0.01), urine protein excretion rate (r=0.754, P<0.01), the number of sclerosing glomeruli (r=0.802, P<0.01) and the area of renal interstitial fibrosis (r=0.797, P<0.01); negative correlation with the level of BMP-7 in blood (r=-0.827, P<0.01), the level of BMP-7 in urine (r=-0.834, P<0.01), the positive area of BMP-7 in renal tissue (r=-0.790, P<0.01), the positive area of BMP-7mRNA in renal tissue (r=-0.790, P<0.01) and Ccr (r=-0.820, P<0.01); no correlation with the level of TGF-beta1 in blood (r=0.066, P=0.540), the level of TGF-beta1 in urine (r=0.052, P=0.630), the positive area of TGF-beta1 in renal tissue (r=0.087, P=0.419) and the positive area of TGF-beta1mRNA in renal tissue (r=0.088, P=0.513).The area of renal interstitial fibrosis had positive correlation with systolic blood pressure (r=0.771, P<0.01), diastolic blood pressure (r=0.771, P<0.01), urine protein excretion rate (r=0.685, P<0.01), the number of sclerosing glomeruli (r=0.833, P<0.01) and the number of crescent (r=0.797, P<0.01); negative correlation with the level of BMP-7 in blood (r=-0.815, P<0.01), the level of BMP-7 in urine (r=-0.776, P<0.01), the positive area of BMP-7 in renal tissue (r=-0.772, P<0.01), the positive area of BMP-7mRNA in renal tissue (r=-0.783, P<0.01) and Ccr (r=-0.798, P<0.01); no correlation with the level of TGF-beta1 in blood (r=0.011, P=0.915), the level of TGF-beta1 in urine (r=0.006, P=0.995), the positive area of TGF-beta1 in renal tissue (r=0.018, P=0.868) and the positive area of TGF-beta1mRNA in renal tissue (r=0.020, P=0.799).Conclusion: In IgA nephropathy, the content of TGF-beta1 in blood and urine and the expression of TGF-beta1 in renal tissue were increased significantly with progressive increase of mesangial proliferation in degree,then decreased significantly with the appearance of renal tubular atropthy and renal interstitial fibrosis.The changes of TGF-beta1 and TGF-beta1 mRNA in blood, urine and renal tissue were positively correlated with urine protein excretion rate, suggesting that TGF-beta1 maybe participate in mesangial proliferation, renal tubular atrophy, glomerulosclerosis and renal interstitial fibrosis in IgA nephropathy. The previous studies showed that BMP-7 as a factor against TGF-beta1,can promote the repair of renal tissue injury and prevent renal fibrosis .In the present study, the content of BMP-7 in blood,urine and renal tissue were all decreased significantly with the aggravation of renal lesions, and had positive correlation with Ccr, negative correlation with other clinical and histological index.Above results indicated that the decrease of BMP-7 content in blood ,urine and renal tissue may be responsible for the development and progression of renal fibrosis in IgA nephropathy. |
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