Expression and significance of P-cadherin,E-cadherin,and β-catenin in colon polyps / 国际检验医学杂志

Objective To explore the expressions and significance of P-cadherin(P-ca),E-cadherin(E-ca), and β-catenin(β-ca)in colon polyps.Methods A total of 120 patients with colon polyps were selected and di-vided into the hyperplastic polyp group(40 cases),the tubular adenoma group(40 cases)and the villous adeno-ma group(40 cases).Other 20 healthy normal persons in the same period were selected as the control group. Immunohistochemistry(S-P)method was used to detect the expressions of P-ca,E-ca,and β-ca of subjects in paraffin sections of colonic polyp tissue and normal colonic mucosa.Western blotting semiquantitative method was used to detect the expression levels of P-ca,E-ca,and β-ca protein.Results P-ca was almost not express-ing in normal colonic mucosa,and positive signals in colon polyps tissue located in the cytoplasm and cell mem-brane,with the progression of the positive expression rate,it gradually increased(P<0.05).Positive-expres-sion of E-ca was in the cell membrane,with the progress of the disease,the positive-expression rate significant-ly decreased(P<0.05),β-ca expressed on the cell membrane in normal colonic mucosa tissue,with cytoplasmic of nuclear ectopic expression in the colon polyps group,with the progress of the disease,the positive rate of cytoplasm of nucleus gradually increased(P<0.05).Conclusion P-ca and β-ca show up-regulated expression in colon polyps,and E-ca show down-regulate expression,these three indicators were related closely to the oc-currence and development of colon polyps.

P-cadherin as myoepithelial cell marker for differential diagnosis of benign and malignant breast lesions.

Background: P-cadherin is cell-cell adhesion glycoprotein which can be used as a myoepithelial cell (MEC) marker in the breast lesions. MEC layer is retained in most benign lesions and loss of this outer layer is hallmark of infiltrating carcinomas in the breast. Aim: To evaluate the expression of P-cadherin as MEC marker in the differential diagnosis of benign and malignant breast lesions. Materials and Methods: Immunohistochemical staining was done using P-cadherin-specific antibody on formalin fixed paraffin-embedded sections of 25 benign and 15 malignant breast lumps. Results: All 25 cases of benign breast lesions showed positive P-cadherin immunostaining, while only 4 out of 15 cases of infiltrating ductal carcinoma showed positive immunostaining for P-cadherin. In the case of benign lesions, staining index varied from 4 to 6 or 7 to 9, while in case of malignant lesions, 11 cases showed staining index from 1 to 3. Only 4 out of 15 malignant cases had staining index from 4 to 6. None of them showed index from 7 to 9. Conclusions: P-cadherin as a MEC marker can be used in differentiating benign and malignant breast lesions.

Effect of Qingre Yiqi Tongluo Preseription on Expressions of P-cadherin and FSP1 in Glomerulus in DN Rats / 浙江中医药大学学报

[Objective]To study the effect of Qingre Yiqi Tongluo(QRYQTL) preseription on proteinria in diabetic nephropathy(DN) rats by means of ob-servation on the expressions of fibroblast-specific protein 1(FSP1) and P-cadherin in in glomerulus in rats.[Methods]60 Sprague-Dawleg rats were divided into normal control group(N), Diabetic nephropathy model group(M), QRYQTL preseription treatment group(Q) and Irbesartan treatment group(I). DN model rats were prepared by intraperitoneal injection with STZ after unilateral nephrectomy. The rats were sacrificed after 12 weeks of the treatment. The creatinine clearance(Ccr),blood urea nitrogen(BUN) and 24h urinary protein(UPro) were tested. Immunohistochemical staining was performed to explore the expressions of P-cadherin and fsp1 in glomerulus.[Results] ①Compared with M group, the levels of 24-hour upro in Q group were significantly de-creased(P<0.01).The levels of Ccr and BUN in Q group were both lower than those of M group( P<0.05). ② Compared with M group, the expressions of P-cadherin in glomerulus in Q group were increased( P<0.01) and the expressions of FSP1 were obviously decreased( P<0.01). The expressions of FSP1 in Q group were decreased compared with that of I groups(P<0.05).[Conclusions]QRYQTL preseription weakened the epithelial-mesenchymal transition (EMT) of podocyte by means of increasing the expression of P-cadherin and reducing the expression of FSP1, thereby decreased the Upro and protect the renal function.

Effect of Puromycin Aminonucleoside on Podocyte P-Cadherin

PURPOSE: To test whether the expression of P-cadherin, a component of slit diaphragms between podocyte foot processes, would be altered by puromycin aminonucleoside (PAN) in a cultured podocyte in vitro. METHODS: Rat glomerular epithelial cells (GEpC) were cultured with various concentrations of PAN. The distribution of P-cadherin was examined with a confocal microscope. Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to measure the change in P-cadherin expression. RESULTS: This study found that P-cadherin was concentrated in the inner and peripheral cytoplasm with high concentrations of PAN under immunofluorescence views. Western blotting of GEpC revealed that PAN induced a decrease of P-cadherin in dose- and time-dependent manners. A high dose (50 microg/mL) of PAN decreased P-cadherin expression by 21.9% at 24 h (P<0.05) and 31.9% at 48 h (P<0.01) compared to those without PAN. In RT-PCR, high concentrations (50 microg/mL) of PAN also decreased P-cadherin mRNA expression, similar to protein suppression, by 23.5% at 48 h (P<0.05). CONCLUSION: Podocytes exposed to PAN in vitro concentrated P-cadherin internally, and reduced P-cadherin mRNA and protein expression. This could explain the development of proteinuria in experimental PAN-induced nephropathy.

The Effect of Cyclosporine on P-cadherin Expression in Experimental Diabetic Nephropathy and Glucose-Stimulated Podocytes / 대한신장학회잡지

PURPOSE: We investigated whether Cyclosporin A (CsA) had the anti-proteinuric effect in diabetic rats and whether it was associated with the alteration of P-cadherin expression. METHODS: Sprague-Dawley rats were injected with diluent (C, N=16) or streptozotocin intraperitoneally (DM, N=16). Eight rats in each group were treated with 10% ethanol or with 1.5 mg/kg/day of CsA (C+CsA and DM+CsA) for 6 weeks. Immortalized mouse podocytes were cultured in media with 5.6 mM glucose (LG), LG+CsA (10-8 M), LG+TGF-beta1, 30 mM glucose (HG), or HG+CsA. Real time-PCR and Western blot were performed for P-cadherin and TGF-beta1 mRNA and protein expression, respectively, with sieved glomeruli and cell lysates. RESULTS: Urinary albumin excretion was significantly higher in DM compared with C rats, and CsA treatment inhibited the increase in albuminuria in DM rats. Glomerular P-cadherin mRNA and protein expression in DM were decreased compared with C rats, and these decreases were significantly inhibited by CsA. Glomerular TGF-beta1 mRNA and protein expression were higher in DM than C rats, and CsA treatment inhibited the increase in TGF-beta1 expression in DM. P-cadherin mRNA and protein expression in HG and LG+TGF-beta1 podocytes were lower than LG cells, and these HG-induced decrements were restored by CsA. CONCLUSION: CsA treatment reduces urinary albumin excretion in DM rats. P-cadherin expression is decreased under diabetic conditions, which is ameliorated by CsA. In addition, inhibition of the increase in glomerular TGF-beta1 expression under diabetic conditions by CsA seems to restore the P-cadherin expression, resulting in the decrease in albuminuria.

High Glucose and Advanced Glycosylation Endproducts(AGE) Modulate the P-cadherin Expression in Glomerular Epithelial Cells(GEpC)

PURPOSE: Podocytes are critical in maintaining the filtration barrier of the glomerulus and are dependent on the integrity of slit diaphragm(SD) proteins including nephrin, P-cadherin, and others. Diabetic proteinuric condition demonstrates defects in SD molecules as well as ultrastructural changes in podocytes. We examined the molecular basis for this alteration of SD molecules especially on P-cadherin as a candidate regulating the modulation of pathogenic changes in the barrier to protein filtration. METHODS: To investigate whether high glucose and AGE induce changes in SD, we cultured rat GEpC under normal(5 mM) or high glucose(30 mM) and AGE- or BSA-added conditions and measured the change of P-cadherin expression by Western blotting and RT- PCR. RESULTS: We found that administration of high glucose decreased the P-cadherin production significantly in the presence or absence of AGE by Western blotting. In RT-PCR high glucose with or without AGE also significantly decreased the expression of P-cadherin mRNA compared to those of controls. Such changes were not seen in the osmotic control. CONCLUSION: We suggest that high glucose with or without AGE suppresses the production of P-cadherin at the transcriptional level and that these changes may explain the functional changes of SD in diabetic conditions.

P-Cadherin is Decreased in Glucose-Stimulated Podocytes and in Experimental Diabetic Nephropathy / 대한신장학회잡지

BACKGROUND: Proteinuria is a cardinal feature of glomerular disease including diabetic nephropathy, and glomerular filtration barrier is considered as a filter restricting protein excretion in urine. We tested whether the expression of P-cadherin, a molecule known to be located at the slit diaphragm, was altered by high glucose in cultured podocytes in vitro and by diabetes in vivo. METHODS: In vitro, immortalized mouse podocytes were cultured in media with 5.6 mM glucose (NG), NG+24.4 mM mannitol (NG+M), or 30 mM glucose (HG) for 7 days at 37dgrees C. Cell lysates were used for RT-PCR and Western blot. For animal studies, twelve Sprague-Dawley rats were injected with diluent (Control, C, N=6) or streptozotocin (DM, N=6) intraperitoneally, and were sacrificed after 6 weeks. RT-PCR and Western blot for P-cadherin mRNA and protein expression, respectively, were performed with sieved glomeruli, and immunohistochemistry with renal tissue. RESULTS: HG significantly reduced P-cadherin mRNA and protein expression in cultured podocytes by 47% and 62%, respectively (p<0.05). Twenty-four hour urinary albumin excretion was significantly higher in DM (12.80+/-1.12 mg/day) compared to C rats (3.15+/-0.24 mg/day) (p<0.05). Glomerular P-cadherin mRNA expression was significantly lower in DM than that in C rats (p<0.05). P-cadherin protein expression assessed by Western blot and immunohistochemistry showed a similar pattern. CONCLUSION: Exposure of podocytes to HG in vitro and diabetes in vivo reduced P-cadherin mRNA and protein expression. These findings suggest that the decrease in P-cadherin expression is connected to the early changes of diabetic nephropathy and thus may contribute to the development of proteinuria.