Chi Young Song

Effects of TGF-beta on podocyte growth and disease progression in proliferative podocytopathies.

Injured podocytes proliferate in cellular focal segmental glomerulosclerosis (FSGS), collapsing FSGS and crescentic glomerulonephritis, where TGF-β1 is overexpressed in hyperplastic podocytes. Yet effects of podocyte TGF-β on podocyte growth and development of glomerulosclerosis have not been clearly defined. TGF-β activates Smads, Ras/extracellular signal-regulated kinase (ERK) and phosphatidyl inositol-3-kinase (PI3K) pathways in podocytes, of which the major TGF-β/Smad signaling pathway appears to override the minor TGF-β-induced Ras/ERK/PI3K pathways. We provide evidence that increasedTGF-β/Smad signaling activity by hyperplastic podocytes may lead to mesangial cell matrix overproduction and eventually to podocyte apoptosis and/or detachment, culminating in the development of glomerulosclerosis. In this regard, TGF-β, which is overexpressed by hyperplastic podocytes, may play an important role for the cellular and collapsing variants of FSGS to evolve into the classic FSGS pattern. In contrast, podocyte proliferation that is induced by Ras/ERK signaling activity in proliferative podocyte diseases seems to be mostly independent of TGF-β1 activity. Collectively, these data bring new insights into our understanding of the overexpression of TGF-β in hyperplastic podocytes in progressive glomerular diseases.

Oxidized Low-Density Lipoprotein and Oxidative Stress in the Development of Glomerulosclerosis

Glomerulosclerosis frequently complicates most renal diseases and is characterized by mesangial matrix accumulation. Oxidized low-density lipoprotein (Ox-LDL) could induce oxidative stress and profibrotic gene expression in mesangial cells. This article will review our current understanding of the pathogenetic mechanisms of lipid-mediated glomerulosclerosis, emphasizing the fibrogenic signaling cascades triggered by Ox-LDL. In addition, therapeutic strategies to prevent the development of Ox-LDL-mediated glomerulosclerosis will be discussed.

mRNA expression of urokinase and plasminogen activator inhibitor-1 in human crescentic glomerulonephritis

mRNA expression of urokinase and plasminogen activator inhibitor‐1 in human crescentic glomerulonephritis