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: A Novel Inhibitor of Homodimerization Targeting MyD88 Ameliorates Renal Interstitial Fibrosis by Counteracting TGF-β1-Induced EMT in Vivo and in Vitro.
    Author: Liu JH, He L, Zou ZM, Ding ZC, Zhang X, Wang H, Zhou P, Xie L, Xing S, Yi CZ.
    Journal: Kidney Blood Press Res; 2018; 43(5):1677-1687. PubMed ID: 30380557.
    Abstract:
    BACKGROUND/AIMS: The TLR/MyD88/NF-κB signaling pathway has been successfully used to treat renal interstitial fibrosis (RIF). However, the exact therapeutic mechanism is still unknown. Here, we assessed the therapeutic efficacy of TJ-M2010-2, a small molecular compound that inhibits MyD88 homodimerization, in RIF induced by ischemia reperfusion injury (IRI). METHODS: In vivo, RIF was induced in mice by IRI, and the mice were prophylactically treated with TJ-M2010-2. In vitro, HK-2 cells were incubated with TGF-β1 to induce EMT, and the cells were pretreated with TJ-M2010-2. RESULTS: We found that, compared with the IRI group, the TJ-M2010-2 group showed marked attenuation of RIF and renal function injury; decreased expression of TGF-β1, α-SMA, vimentin, MMP2 and MMP9; and increased E-cadherin expression. Furthermore, TGF-β1-induced EMT was blocked by TJ-M2010-2 in HK-2 cells, as evidenced by blocked morphologic transformation, restored E-cadherin expression and inhibited α-SMA expression. In addition, compared to the TGF-β1 group, the TJ-M2010-2 group showed profound inhibition of the expression of TRAF6, p65 and Snail and upregulation of the expression of IκBα. CONCLUSION: This MyD88 inhibitor may be a potential therapeutic agent to ameliorate RIF.
    [Abstract] [Full Text] [Related] [New Search]