title: Effects of TGF-beta on podocyte growth and disease progression in proliferative podocytopathies.
abstract: Injured podocytes proliferate in cellular focal segmental glomerulosclerosis (FSGS), collapsing FSGS and crescentic glomerulonephritis, where TGF-beta(1) is overexpressed in hyperplastic podocytes. Yet effects of podocyte TGF-beta on podocyte growth and development of glomerulosclerosis have not been clearly defined. TGF-beta activates Smads, Ras/extracellular signal-regulated kinase (ERK) and phosphatidyl inositol-3-kinase (PI3K) pathways in podocytes, of which the major TGF-beta/Smad signaling pathway appears to override the minor TGF-beta-induced Ras/ERK/PI3K pathways. We provide evidence that increasedTGF-beta/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-beta, 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-beta(1) activity. Collectively, these data bring new insights into our understanding of the overexpression of TGF-beta in hyperplastic podocytes in progressive glomerular diseases.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. hyunsoon@plaza.snu.ac.kr
authors.forename: Hyun Soon
authors.initials: HS
authors.lastname: Lee
authors.forename: Chi Young
authors.initials: CY
authors.lastname: Song
mesh_terms: D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D050199:Podocytes / Q000473:pathology* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta