The Long Noncoding RNA Meg3 Mediates TLR4-induced Inflammation in Experimental Obstructive Nephropathy

Overview

Journal Clin Sci (Lond)

Specialties Biochemistry
General Medicine
Science

Date 2023 Jan 27

PMID 36705251

Authors

Wai Han Yiu

Sarah W Y Lok

Rui Xue

Jiaoyi Chen

Kar Neng Lai

Hui Yao Lan

Sydney C W Tang

Affiliations

Soon will be listed here.

Abstract

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.

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