Ablation of lncRNA MIAT mitigates high glucose-stimulated inflammation and apoptosis of podocyte via miR-130a-3p/TLR4 signaling axis.

Podocyte injury has been considered as a major contributor to the progression of diabetic nephropathy (DN). Long non-coding RNAs (lncRNAs) are being found to be involved in DN pathogenesis. The current research was designed to elucidate the potential role and latent molecular mechanism of long non-coding RNA MIAT in HG-induced podocyte injury. Our data demonstrated that MIAT expression was substantially elevated but miR-130a-3p was diminished in HG-challenged podocytes. Additionally, lack of MIAT mitigated HG-evoked inflammatory reaction in podocytes as evidenced by the diminished the release of inflammatory mediators TNF-α, IL-6 and IL-1β. Moreover, depletion of MIAT evidently amplified cell viability and alleviated HG-triggered apoptosis, reflected as the downregulation of Bax expression concomitant with the enhancement of Bcl-2 expression in HG-exposed podocytes. Mechanistically, MIAT effectively modulated TLR4 expression through acting as a competing endogenous sponge of miR-130a-3p, and TLR4 was confirmed as a specific target gene of miR-130a-3p. More importantly, the miR-130a-3p/TLR4 crosstalk contributed to the protective effect of MIAT knockdown on HG-provoked podocyte damage. Collectively, these findings highlighted that blocking MIAT/miR-130a-3p/TLR4 network play vital regulatory roles in mitigating HG-induced inflammation damage and apoptosis, thereby protecting podocyte from HG-stimulated injury, implying that MIAT might be a promising therapeutic strategy for developing effective treatments against DN progression.

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