title: FK506 inhibits the mice glomerular mesangial cells proliferation by affecting the transforming growth factor-β and Smads signal pathways.
abstract: Abstract TGF-β1 plays an important role in the pathogenesis of chronic renal diseases. Although the specific mechanism is unknown, a major factor is the potent fibrogenic activity of TGF-β1 in the chronic progression of renal diseases. TGF-β1 closely correlates with renal fibrosis in cooperation with several fibrosis-promoting molecules. Recently it has been studied that, Smad proteins as intracellular mediators of TGF-β signaling pathways provide important insights into the mechanisms determining the specificity of TGF-β action in various renal cells. Some studies have proved that immunosuppressants can affect TGF-β expression, but the mechanisms are unclear. In this study, we investigated the effect of FK506 on mesangial cells via TGF-β and Smads signal pathways. Our results shows that FK506 effectively blocked the TGF-β/Smad signaling pathway by downregulation of TGF-β receptor, and played an important role in TGF-β1-induced Smad2 expression in mice mesangial cells. FK506 can inhibit the TGF-β1-stimulated cell proliferation via Smad-related pathways. And reduced the Smad2 protein and mRNA expression. Altogether, this study provided a theoretical proof for the protective and treating effect of FK506 on kidneys.
authors: Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou, Guangdong Province , China .
authors: Ren
authors: R
authors: Qi
authors: Wen
authors: W
authors: Li
authors: Shengyou
authors: S
authors: Yu
mesh_terms: D000818:Animals; D065095:Calcineurin Inhibitors / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D065095:Calcineurin Inhibitors; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; D016559:Tacrolimus