| RRC ID |
77003
|
| 著者 |
Wang M, Zhang Q, Lou S, Jin L, Wu G, Wu W, Tang Q, Wang Y, Long X, Huang P, Luo W, Liang G.
|
| タイトル |
Inhibition of MD2 by natural product-drived JM-9 attenuates renal inflammation and diabetic nephropathy in mice.
|
| ジャーナル |
Biomed Pharmacother
|
| Abstract |
Diabetic kidney disease (DKD) is one of the severe complications of diabetes mellitus-related microvascular lesions, which remains the leading cause of end-stage kidney disease. The genesis and development of DKD is closely related to inflammation. Myeloid differentiation 2 (MD2) mediates hyperlyciemia-induced renal inflammation and DKD development and is considered as a potential therapeutic target of DKD. Here, we identified a new small-molecule MD2 inhibitor, JM-9. In vitro, JM-9 suppressed high glucose (HG) and palmitic acid (PA)-induced inflammation in MPMs, accompanied by inhibition of MD2 activation and the downstream TLR4/MyD88-MAPKs/NFκB pro-inflammatory signaling pathway. Macrophage-derived factors increased the fibrotic and inflammatory responses in renal tubular epithelial cells, which were inhibited by treating macrophages with JM-9. Then, we investigated the therapeutic effects against DKD in streptozotocin-induced type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) mouse models. Treatment with JM-9 prevented renal inflammation, fibrosis, and dysfunction by targeting MD2 in both T1DM and T2DM models. Our results show that JM-9, a new small-molecule MD2 inhibitor, protects against DKD by targeting MD2 and inhibiting MD2-mediated inflammation. In summary, JM-9 is a potential therapeutic agent for DKD.
|
| 巻・号 |
168
|
| ページ |
115660
|
| 公開日 |
2023-10-6
|
| DOI |
10.1016/j.biopha.2023.115660
|
| PII |
S0753-3322(23)01458-0
|
| PMID |
37806092
|
| IF |
4.545
|
| リソース情報 |
| 実験動物マウス |
RBRC02388 |
