u-0126 and Glomerulonephritis--IGA

Immunoglobulin A nephropathy (IgAN) is one of the most common glomerular diseases worldwide. Various studies have identified a host of microRNAs (miRNAs) abnormally expressed in IgAN and might affect the pathogenesis and progression of IgAN. However, miR-200bc/429 cluster in the pathopoiesis of IgAN remains poorly understood. For this study, we found that miR-200bc/429 cluster is downregulated in IgAN tissues and IgAN podocytes and HK2 cells compared with their matched controls respectively. In addition, overexpression of miR-200bc/429 cluster in IgAN podocytes and HK2 cells could attenuate the release of inflammatory cytokines MCP-1, IL-6 and RANTES. Moreover, the 3' untranslated region (UTR) of TNF-like weak inducer of apoptosis (TWEAK) was identified to be a direct target of miR-200bc/429 cluster. Furthermore, our results showed that miR-200bc/429 cluster can inhibit TWEAK mediated NF-κB pathway activation in IgAN. Overall, our findings revealed that miR-200bc/429 cluster alleviates inflammation in IgAN through TWEAK/Fn14 system and might serve as a biomarker as well as a promising therapeutic target for IgAN.

Topics: Aminosalicylic Acids; Animals; Apoptosis; Benzenesulfonates; Butadienes; Cell Line; Cytokine TWEAK; Glomerulonephritis, IGA; Glycation End Products, Advanced; Inflammation; Interleukin-6; MAP Kinase Signaling System; Mice; MicroRNAs; Nitriles; Osteocytes; p38 Mitogen-Activated Protein Kinases; STAT3 Transcription Factor; Vascular Endothelial Growth Factor A