Background: Podocyte injury plays an important role in glomerulosclerosis in IgA nephropathy (IgAN). Eepithelial-to-mesenchymal transition (EMT) caused by different factors is the main reason for podocyte damage. This study hypothesized that conditioned mesangial medium may induced EMT process of podocytes and thereby lead to glomerular injury or sclerosis. Materials and Methods: Podocytes were incubated in medium from mesangial cells incubated with aggregated IgA1(aIgA1) isolated from IgAN patients. Wortmannin were used to inhibit phosphatidylinositol-3-kinase (PI3-K) in podocytes. Results: Western blot analysis, real-time PCR and confocal fluorescent microscopy demonstrated that reduced expression of P-Cadherin, Zonula occludens-1 (ZO-1) and podocin, increased expression of fibroblast –specific protein (FSP-1), α-smooth muscle action(α-SMA) and desmin in podocytes exposed to medium from mesangial cells incubated with aIgA1 isolated from IgAN patients compared with podocytes cultured in RPMI 1640 medium containing 0.5% fetal bovine serum ( FBS) (p<0.05). Mesangial medium resulted in a greater albumin influx across the podocyte monolayer (p<0.05). Phosphorylation of Akt increased with this medium, as indicated by an increase in the p-Akt/Akt ratio. Treatment with wortmannin partly restored the changes in epithelial and mesenchymal markers and albumin influx. IgAN patients with massive proteinuria showed remarkable α-SMA and FSP-1 expression in podocytes. Conclusion: Our findings indicated that mesangial medium from cells incubated with aIgA1 isolated from IgAN patients induced EMT in podocytes and the PI3-K/ Akt-signaling pathway was involved in the process.
Based on GM yield criterion, the analytical solutions for shape and size of mode I crack tip plastic zone and the burst pressure for X70 pipeline steel are derived. Comparing the solutions with those based on Mises and Trasca criteria shows that under plain strain condition the area of plastic zone on GM is between Tresca and Mises solutions, and very close to Mises one. Among the areas Tresca’s is the largest and Mises is the smallest and all three zones are dumbbell shaped. However, for pipeline burst pressure based on Tresca criterion is the smallest and that on Twin shear stress criterion (TSS) is the largest, those on GM and Mises are also very close to each other and lie between Tresca and TSS results.
A new linear yield criterion, referred to as Equal Area (EA) yield criterion, was derived in Haigh Westergaard stress space based on the projection area of its yielding locus on the π-plane equal to the area of von Mises yielding circle. Under the plane stress and strain conditions the crack tip plastic zone dimensions were calculated based on EA yield criterion and compared with those calculated according to the Tresca and von Mises yield criteria. The results showed that the crack tip plastic zone based on EA yield criterion is similar to that based on von Mises yield criterion, but is much different to that based on Tresca yield criterion. Meanwhile, the influences of Poisson ratio and loading parameter on the crack tip plastic zone were investigated based on EA yield criterion.
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