Mechanisms and consequences of TGF-ß overexpression by podocytes in progressive podocyte disease

In patients with progressive podocyte disease, such as focal segmental glomerulosclerosis (FSGS) and membranous nephropathy, upregulation of transforming growth factor-ß (TGF-ß) is observed in podocytes. Mechanical pressure or biomechanical strain in podocytopathies may cause overexpression of TGF-ß and angiotensin II (Ang II). Oxidative stress induced by Ang II may activate the latent TGF-ß, which then activates Smads and Ras/extracellular signal-regulated kinase (ERK) signaling pathways in podocytes. Enhanced TGF-ß activity in podocytes may lead to thickening of the glomerular basement membrane (GBM) by overproduction of GBM proteins and impaired GBM degradation in podocyte disease. It may also lead to podocyte apoptosis and detachment from the GBM, and epithelial-mesenchymal transition (EMT) of podocytes, initiating the development of glomerulosclerosis. Furthermore, activated TGF-ß/Smad signaling by podocytes may induce connective tissue growth factor and vascular endothelial growth factor overexpression, which could act as a paracrine effector mechanism on mesangial cells to stimulate mesangial matrix synthesis. In proliferative podocytopathies, such as cellular or collapsing FSGS, TGF-ß-induced ERK activation may play a role in podocyte proliferation, possibly via TGF-ß-induced EMT of podocytes. Collectively, these data bring new mechanistic insights into our understanding of the TGF-ß overexpression by podocytes in progressive podocyte disease

An experimental and modeling study of synthesis, consolidation and aging behavior of AA2014 composite reinforced by TiB2 via powder metallurgy method

Aluminum 2014 alloy composite reinforced with TiB2 particulates with different volume% of TiB2 (5, 10 and 15%) has been successfully synthesized by P/M route. The composite powders were consolidated by cold uniaxial compaction pressure followed by sintering at 590 °C in N2 atmosphere. The Al 2014–TiB2 composites were aged at 160 °C between 0 and 8 h followed by microstructural characterization and hardness evaluation. Scheil cooling and equilibrium calculations were performed using FactSage for qualitative understanding of the microstructural evolution during sintering and aging operations. In addition, the thermo-physical properties such as hardness, density and transverse rupture strength of the sintered samples were evaluated.Rana Pratap Singh, Gaurav Kumar Gupta and Manas Paliwa