Prolonged renal inflammation contributes to fibrosis, which may eventually lead to irreversible chronic kidney disease. Our previous work demonstrated that LIM and cysteine-rich domain 1 (LMCD1) are associated with renal interstitial fibrosis in a 21-day unilateral ureteral obstruction (21UUO) mouse model. Interestingly, based on the gene expression omnibus database, we found that LMCD1 is enhanced in the mouse kidney as early as 5, 7, and 10?days following unilateral ureteral obstruction (UUO), suggesting that LMCD1 may exert its function in an earlier phase. To validate this conjecture, a 7UUO mouse model and a tumor necrosis factor-α (TNF-α)-stimulated HK-2 cell model were established, followed by injection of adenovirus vectors carrying short hairpin RNA targeting LMCD1. LMCD1 silencing ameliorated renal collagen deposition and reduced the expression of profibrotic factors in the 7UUO model. LMCD1 silencing alleviated tubulointerstitial inflammation by mitigating F4/80 + cell infiltration, monocyte chemoattractant protein-1 release and nuclear factor-κB activation. In addition, LMCD1 silencing suppressed NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and nuclear factor of activated T cells 1 (NFATc1) nuclear translocation. Consistent results were obtained in TNF-α-stimulated HK-2 cells in vitro . Mechanistically, the transcriptional coactivator LMCD1 cooperates with the transcription factor NFATc1 to increase NLRP3 expression. Collectively, these findings suggest that LMCD1 participates in tubulointerstitial inflammation via an LMCD1-NFATc1/NLRP3 mechanism. LMCD1 may therefore become a potential target for the control of renal inflammation and fibrosis.
文章引用产品列表
-
- EK287
- ELISA试剂盒
Mouse CCL2/MCP-1 ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥2,650.00
-
- EK287HS
- 高敏试剂盒
Mouse CCL2/MCP-1 High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK218
- ELISA试剂盒
Mouse IL-18 ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥2,650.00
-
- EK201BHS
- 高敏试剂盒
Mouse IL-1β High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK201B
- ELISA试剂盒
Mouse IL-1β ELISA Kit 检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00
-
- EK187
- ELISA试剂盒
Human MCP-1/CCL2 ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥2,650.00
-
- EK118
- ELISA试剂盒
Human IL-18 ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥2,650.00
-
- EK101B
- ELISA试剂盒
Human IL-1β ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00
-
- EK101BHS
- 高敏试剂盒
Human IL-1β High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00