These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Ubiquitination and regulation of Smad7 in the TGF-β1/Smad signaling of aristolochic acid nephropathy.
    Author: Tian Y, Liao F, Wu G, Chang D, Yang Y, Dong X, Zhang Z, Zhang Y, Wu G.
    Journal: Toxicol Mech Methods; 2015; 25(8):645-52. PubMed ID: 26108275.
    Abstract:
    Aristolochic acid I (AAI) affects TGF-β1/Smad signaling, which causes AA nephropathy (AAN), but the mechanisms are not fully understood. We aimed to clarify whether Arkadia and UCH37 participate in TGF-β1/Smad signaling via Smad7, and the regulatory mechanisms of Smad7. One side, mice and cultured mouse renal tubular epithelial cells (RTECs) were treated with various AAI doses and concentrations, respectively; on the other side, RTECs were transfected with small interfering RNA (siRNA) expression vectors against Arkadia and UCH37 and then treated with 10 µg/ml AAI. And then detect the mRNA and protein levels of Smad7, UCH37, Arkadia and any other relative factors by RT-PCR and Western blotting. In kidney tissues and RTECs, the mRNA and protein levels of Smad7 decreased with increasing AAI doses concentrations by real-time PCR and Western blotting, whereas those of Arkadia, UCH37, Smad2, Smad3 and TβRI increased. Cells transfected with the Arkadia siRNA expression vector showed reduced mRNA and protein levels of vimentin, α-SMA, Smad2, Smad3 and TβRI after AAI treatment, while those of CK18 and Smad7 increased compared with those of untransfected RTECs. Conversely, cells transfected with the UCH37 siRNA expression vector showed the opposite effect on analyzed signaling molecules after AAI treatment. Arkadia and UCH37 participate in TGF-β1/Smad signaling-mediated renal fibrosis, and Smad7 blocks TGF-β1 signaling by inhibiting Smad2/Smad3 phosphorylation and enhancing the degradation of TβRI.
    [Abstract] [Full Text] [Related] [New Search]