HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

Pathogenic role of TGF-ß in the progression of podocyte diseases

Hyun Soon Lee

Department of Pathology, Seoul National University College of Medicine, Chongno-gu, Seoul, Korea.

Offprint requests to: Hyun Soon Lee, M.D., Department of Pathology, Seoul National University College of Medicine, Chongno-gu, Yongon-dong 28, Seoul 110-799, Korea. e-mail: hyunsoon@plaza.snu.ac.kr


Summary. In patients with progressive podocyte diseases, such as focal segmental glomerulosclerosis and membranous nephropathy, there is enhanced expression of transforming growth factor (TGF-ß) in podocytes. Biomechanical strain in these diseases may cause overexpression of TGF-ß and angiotensin II (Ang II) by podocytes. Oxidative stress induced by Ang II may activate the latent TGF-ß. Increased TGF-ß activity by podocytes may induce not only the thickening of the glomerular basement membrane (GBM), but also podocyte apoptosis and/or detachment from the GBM, initiating the development of glomerulosclerosis. Furthermore, mesangial matrix expansion frequently occurs in podocyte diseases in association with the development of glomerulosclerosis. This review examines open questions on the pathogenic role of TGF-ß that links podocyte injury to GBM thickening, podocyte loss, mesangial matrix expansion and glomerulosclerosis in podocyte diseases. It also describes paracrine regulatory mechanisms of podocyte TGF-ß on mesangial cells leading to increased matrix synthesis
. Histol Histopathol 26, 107-116 (2011)

Key words: Angiotensin II, Biomechanical strain, Glomerular basement membrane thickening, Mesangial matrix expansion, Oxidative stress, Podocyte apoptosis

DOI: 10.14670/HH-26.107