| Objective: The prognosis of IgA Nephropathy (IgAN) has correlation with glomerular sclerosis,hypertension,severity of proteinuria,renal function impairment, also closely with renal interstitial fibrosis(RIF). Phosphase and tensin homology deleted on chromosome 10(PTEN), downregulated by TGF-β, can inhibit cell proliferation and induce apoptosis. Substantial evidence suggests the roles of PTEN in the development of idiopathic pulmonary fibrosis, rheumatoid arthritis and Diabetic Nephropathy. But the relationship between PTEN and RIF remains unknown. Our studies examined the potential correlation between the expression of PTEN and RIF in IgA nephropathy.Methods: Forty-seven patients diagnosed as primary IgA nephropathy by renal pathology at the second affiliated hospital of Hebei Medical University were involved in this study. All patients were not treated with glucocorticosteroid,cytotoxic drug,ACEI and ARB. Patients with Henoch-Schonlein Nephritis,Lupus Nephritis,HBV-GN associated glomerulonephritis,hepatic cirrhosis glomerulopathy,psoriasis associated glomerulonephritis,thyropathy,renal damage induced by rheumatoid arthritis and cancer associated nephropathy were excluded. Patients complicating acute renal tubular necrosis,acute or chronic interstitial nephritis also need to be excluded. 10 specimens from normal renal tissue of renal carcinoma as control group. All tissue were diagnosed as normal which evaluated by light microscopy and immunofluorescence. Tubulointerstitial lesion(TIL) was classified by using Katafuchi scale, including no TIL(Group I), mild TIL(Group II), moderate TIL(Group III) and severe TIL(Group IV). The expression of PTEN,TGF-β1,α-SMA and ColⅢin renal tissue were detected by immunohistochemistry, PTENmRNA were detected by in situ hybridization. The semi-quantitative analysis of renal tissue immunohistochemistry and in situ hybridization results were measured applicating Beihang IMS-2000 image analysis system. Collecting detailed clinical and pathological data.Results:①Clinical data: With the progress of RIF in IgA nephropathy, eGFR and urine osmotic pressure were gradually decreased from Group I to Group IV (P<0.05); UPE in Group IV was higher than in Group I and Group II (P<0.05); the rate of sclerosis glomeruli in Group III and Group IV was obviously higher than in Group I and Group II, and the rate of sclerosis glomeruli in Group IV was also higher than in Group III (P<0.05); the scores of vascular lesion in Group III and Group IV was obviously higher than in Group I and Group II, and the scores of vascular lesion in Group IV was also higher than in Group III (P<0.05).②The expression of PTEN and PTENmRNA in renal tissues of IgAN: Renal tissues from renal biopsy in control group and IgAN groups show abundant expression of PTEN in endochylema of renal tubular epithelial cell, negligible expression in glomeruli, and no expression in renal interstitium, blood vessel and inflammatory cells; The expression of PTENmRNA was similar with PTEN, and little expression in the nucleus of renal tubular epithelial cells. In control group and Group I, there are expression of PTEN and PTENmRNA in the cytoplasm of almost every tubular epithelial cells(P>0.05); With the progress of RIF in IgA nephropathy, the expression of PTEN and PTEN mRNA decreased gradually (12.23±1.4,12.55±1.35;10.04±1.14,10.38±1.36;8.00±1.98,8.06±2.21)%, there was significant differences in three groups(P<0.05).③The expression of TGF-β1,α-SMA and ColⅢin renal tissues of IgAN: In control group and Group I, TGF-β1 expressed mainly in cavosurface of renal tubular epithelial cell, but little in glomeruli, there was no difference between the groups(P>0.05); With the progress of RIF in IgA nephropathy, TGF-β1 in addition to the expression of renal tubular epithelial cells, also have a certain expression in renal interstitium, inflammatory cells surrounding renal glomeruli and tubules regions and mesangial cells, and the expression of TGF-β1 was significantly increased(9.62±1.82,11.43±1.75, 13.20±1.68)%; there were significant differences among three groups (P<0.05).In control and Group I,α-SMA expressed mainly in renal vascular smooth muscle wall, occasionally in renal interstitium, there was no difference between the groups(P>0.05); With the progress of RIF in IgA nephropathy,α-SMA widely expressed in interstitium and endochylema of renal tubular epithelial cell,even in glomerular mesangial region(7.85±0.84, 9.40±0.93, 10.90±2.00)%, there was significant differences among the three groups, and compared with control group and Group I (P<0.05). In control group and Group I, ColⅢexpressed mainly in renal interstitium, there was no difference between the groups(P>0.05); With the progress of RIF in IgA nephropathy, the expression of ColⅢincreased gradually, occasionally little in renal tubular epithelial cell, there was significant differences among the three groups (P<0.05).④The correlation between pathological and clinical data: The expression of PTEN and PTENmRNA in renal tissues has positive correlations with eGFR(r =0.791,0.811;P<0.01), with urine osmotic pressure(r =0.739,0.720; P<0.01); negative correlations with the expression of TGF-β1(r =-0.632, -0.614; P<0.01), with the expression ofα-SMA(r =-0.669, -0.627; P<0.01), with the expression of ColⅢ(r =-0.656, -0.657; P<0.01), with urinary protein excretion for 24 hours(r =-0.523, -0.606; P<0.01), with the rate of sclerosis glomeruli(r =-0.775, -0.776; P<0.01), with the scores of vascular lesion(r =-0.850,-0.776;P<0.01).Conclusion:①With the increase of TIL in IgAN, the expression of PTEN was gradually decreased, even deletion; These suggested that PTEN may be an anti-fibrosis endogenous protection element in RIF of IgA nephropathy.②Moreover, TGF-βsignaling induces epithelial to mesenchymal transition and extracellular matrix accumulation possibly through a mechanism dependent on the downregulation of PTENmRNA.
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