| First Author | Yiu WH | Year | 2023 |
| Journal | Clin Sci (Lond) | Volume | 137 |
| Issue | 5 | Pages | 317-331 |
| PubMed ID | 36705251 | Mgi Jnum | J:355557 |
| Mgi Id | MGI:7715042 | Doi | 10.1042/CS20220537 |
| Citation | Yiu WH, et al. (2023) The long noncoding RNA Meg3 mediates TLR4-induced inflammation in experimental obstructive nephropathy. Clin Sci (Lond) 137(5):317-331 |
| abstractText | Kidney inflammation contributes to the progression of chronic kidney disease (CKD). Modulation of Toll-like receptor 4 (TLR4) signaling is a potential therapeutic strategy for this pathology, but the regulatory mechanisms of TLR4 signaling in kidney tubular inflammation remains unclear. Here, we demonstrated that tubule-specific deletion of TLR4 in mice conferred protection against obstruction-induced kidney injury, with reduction in inflammatory cytokine production, macrophage infiltration and kidney fibrosis. Transcriptome analysis revealed a marked down-regulation of long noncoding RNA (lncRNA) Meg3 in the obstructed kidney from tubule-specific TLR4 knockout mice compared with wild-type control. Meg3 was also induced by lipopolysaccharide in tubular epithelial cells via a p53-dependent signaling pathway. Silencing of Meg3 suppressed LPS-induced cytokine production of CCL-2 and CXCL-2 and the activation of p38 MAPK pathway in vitro and ameliorated kidney fibrosis in mice with obstructive nephropathy. Together, these findings identify a proinflammatory role of lncRNA Meg3 in CKD and suggest a novel regulatory pathway in TLR4-driven inflammatory responses in tubular epithelial cells. |
