Mechanism of LncRNAHOTAIR in promoting progression of lupus nephritis by targeting miR-17-5p/TXNIP
Objective To investigate the mechanism of long non-coding RNA metastasis homeobox transcript antisense RNA (Ln-cRNA HOTAIR) in promoting the progression of lupus nephritis (LN) by targeting the miR-17-5p/thioredoxin interacting protein (TXNIP) axis. Methods Sixty MRL/lpr female mice were randomly separated into the model group,LncRNAHOTAIR knockdown group,miR-17-5p agamir,negative control group,and LncRNAHOTAIR knockdown+miR-17-5p agamir group,with 12 mice in each group,and another 12 C57BL/6J female mice were collected as the control group. After grouping and intervention treatment,renal function,and immune organ index of mice in each group were detected;HE staining experiment was applied to detect the pathological morphology of kidney tissue of mice in each group;enzyme-linked immunosorbent assay (ELASA) method was applied to measure the serum levels of anti double stranded DNA (dsDNA) and immune cytokines such as immunoglobulin G (IgG),interleukin-6 (IL-6),monocyte chemotactic protein-1 (MCP-1),and tumor necrosis factor-α (TNF-α) of mice in each group;quantitative real-time PCRpolymerase chain reaction (qPCR) and immunoblotting experiments were applied to detect the expression of LncRNAHOTAIR,miR-17-5p,and TXNIP in the kidney tissue of mice in each group. Dual luciferase re-porter gene experiment was applied to detect the targeted regulation of LncRNAHOTAIR on miR-17-5p,and miR-17-5p on TXNIP in mouse mesangial cells. Results Compared with the control group,the kidney tissue of mice in the model group experienced severe pathological dam-age,the thymus index,spleen index,and miR-17-5p expression decreased (P＜0.05),and the urinary protein concentration,blood urea nitro-gen (BUN) level,serum anti-dsDNA and IgG,IL-6,MCP-1,TNF-α levels,and renal tissue LncRNAHOTAIR and TXNIP expression in-creased (P＜0.05). Compared with the model group,the pathological damage to the kidney tissue of mice in the LncRNAHOTAIR knockdown group and miR-17-5p agomir group was reduced,the thymus index,spleen index,and miR-17-5p expression increased (P＜0.05),and the uri-nary protein concentration,BUN level,serum anti-dsDNA and IgG,IL-6,MCP-1,TNF-α levels,and renal tissue LncRNAHOTAIR and TXNIP expression decreased (P＜0.05). Downregulating miR-17-5p could weaken the effects of knocking down LncRNAHOTAIR on various indicators in the model group mice. Conclusions Knocking down LncRNA HOTAIR can reduce TXNIP expression by up-regulating miR-17-5p,thereby reducing the production of immune inflammatory factors in LN mice,enhancing their immune function,inhibiting the occur-rence and development of inflammation in vivo,and ultimately reducing renal tissue damage in mice and improving their renal function.
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