科研之友
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摘要
Background/Aims: The TLR/MyD88/NE-KB 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 (IRO. 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-p1 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 TGE-beta 1, a-SMA, vimentin. MMP2 and MMP9; and increased E-cadherin expression. Furthermore, TGF-beta 1-induced EMT was blocked by TJ-M2010'2 in HK-2 cells, as evidenced by blocked morphologic transformation, restored E-cadherin expression and inhibited a-SMA expression. In addition, compared to the TGF-p1 group, the TJ-M2010-2 group showed profound inhibition of the expression of TRAF6, p65 and Snail and upregulation of the expression of IKBa. Conclusion: This MyD88 inhibitor may be a potential therapeutic agent to ameliorate RIF.
