| Objective To investigate the mechanism of long non-coding RNA metastasis homeobox transcript antisense RNA (LncRNA 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 reporter 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 damage, the thymus index, spleen index, and miR-17-5p expression decreased (P<0.05), and the urinary protein concentration, blood urea nitrogen (BUN) level, serum anti-dsDNA and IgG, IL-6, MCP-1, TNF-α levels, and renal tissue LncRNAHOTAIR and TXNIP expression increased (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 urinary 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 occurrence and development of inflammation in vivo, and ultimately reducing renal tissue damage in mice and improving their renal function. |
