S-Space College of Medicine/School of Medicine (의과대학/대학원) Pathology (병리학전공) Journal Papers (저널논문_병리학전공)
Differential role of mesangial cells and podocytes in TGF-beta-induced mesangial matrix synthesis in chronic glomerular disease
- Lee, Hyun Soon; Song, Chi Young
- Issue Date
- F HERNANDEZ
- HISTOLOGY AND HISTOPATHOLOGY; Vol.24 7; 901-908
- Chronic glomerular disease; TGF-beta activation; Podocytes; Glomerulosclerosis; Mesangial matrix
- Glomerulosclerosis is characterized by mesangial matrix accumulation that is mediated primarily by activation of transforming growth factor-beta (TGF-beta). Unlike podocytes, mesangial cells secrete TGF-beta in response to common in vitro fibrogenic stimuli. However, mesangial immunostaining for active TGF-beta 1 in chronic glomerular disease is almost negligible, despite increased mesangial TGF-beta 1 mRNA expression, while podocytes covering the sclerotic glomerular segments exhibit increased TGF-beta 1 protein expression. The mechanisms whereby TGF-beta is activated in the diseased glomeruli and how the activated TGF-beta leads to mesangial matrix overproduction are not clear. We provide evidence that TGF-beta secreted as latent complexes by mesangial cells is stored in the mesangial matrix, from which soluble forms of latent TGF-beta are released and localized to the podocyte surface in chronic glomerular disease. Podocyte-derived reactive oxygen species, plasmin and thrombospondin-1, particularly renin-angiotensin-aldosterone system-induced oxidative stress, seem to be involved in TGF-beta activation in podocytes. We also provide evidence that the TGF-beta-induced secretion of connective tissue growth factor and vascular endothelial growth factor by podocytes acts as a paracrine regulatory mechanism on mesangial cells, which may cause mesangial matrix accumulation culminating in the development of glomerulosclerosis. Collectively, these data bring new insights into our understanding of the roles of the mesangial cells and podocytes in the TGF-beta-induced mesangial matrix synthesis in chronic glomerular disease.
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