TGF-beta and glomerulonephritis: anti-inflammatory versus prosclerotic actions

Abstract

TGF-beta has been considered as the key regulator in the generation of glomerulosclerosis. Despite abundant descriptive data, it still remains undetermined whether sustained, local expression of TGF-beta leads to irreversible glomerulosclerosis. There is no doubt that TGF-beta stimulates ECM production in the glomerulus, but this molecule has several anti-inflammatory properties as well. Towards a better understanding of the pathogenesis of glomerulonephritis and for the development of novel and efficient therapeutic interventions, extensive efforts should be made to clarify the 'bright side' of TGF-beta as well as its 'dark side' in individual experimental and human diseases, focusing especially on the concentration and the time-point at which its anti-inflammatory properties spill over into its prosclerotic actions.

GVHD-associated chronic kidney disease after allogeneic haematopoietic cell transplantation

“…Injury of the endothelium, the principal target tissue of cGVHD, may initially lead to inflammation, cytokine cascade through tumor necrosis factor-a (TNF-a), IL-6 and transforming growth factor-b (TGFb) and later to fibrosis and organ failure as a result of the immune intolerance of cGVHD. [22][23][24][25][26][27][28] In the case of CKD, enhanced alloimmunity and cellular cytokine storm due to GVHD may promote renal fibrogenesis, which is generated by a tissue environment invaded by inflammatory cells.…”

Chronic Kidney Disease in Long-Term Survivors of Hematopoietic Cell Transplantation

“…In addition to the T cell activation and cytokine release in acute GVHD, chronic GVHD involves the activation of B cells and production of cytokines, including TGF-␤1 (81). TGF-␤1 is important for collagen synthesis and matrix deposition in the kidney and other organs (82,83) and also may be important in the development of cyclosporine nephropathy in nonrenal transplant patients (84). The effects of cyclosporine on the kidney can be potentiated by increases in the production of TGF-␤ (85).…”

Cytoskeletal Rearrangement and Signal Transduction in TGF-β1–Stimulated Mesangial Cell Collagen Accumulation

“…The central role of TGF-␤ in the pathogenesis of glomerulosclerosis is supported by studies of human kidney diseases and animal models (1,2). TGF-␤ overexpression causes glomerulosclerosis in transgenic mice (3), whereas extracellular matrix (ECM) accumulation in the acute anti-Thy-1 nephritis model is diminished by the administration of anti-TGF-␤ serum (4); decorin, a natural TGF-␤ inhibitor (5); or oligodeoxynucleotides antisense to TGF-␤ (6).…”