MiR-130a protects against lipopolysaccharide-induced glomerular cell injury by upregulation of Klotho.

ABSTRACT

AIMS: Lupus nephritis is a frequent and serious complication of systemic lupus erythematosus (SLE). Therefore, better understanding regarding the underlying mechanism of renal tubular injury induced by SLE, is beneficial to develop different therapeutic strategies for lupus nephritis. The study aimed to investigate the role of miR-130a against lipopolysaccharide-induced glomerular cell injury. METHODS: HK-2 cells (human renal proximal tubule cells) were used for detecting miR-130a levels. Cells were divided into scramble, miR-130 mimic, siNC, si-miR-130a and si-Klotho groups apoptosis and CCK-8 assays were performed to investigate the cell apoptosis and proliferation rates. qRT-PCR, ELISA, and western blotting were performed to detect the proteins and their expressions. RESULTS: LPS induced inflammatory injury in HK-2 cells by inducing cell apoptosis (P < 0.01) and by expressing the inflammatory factors such as IL-1ß, IL-6, IL-8 and TNF-α in HK-2 cells. LPS increased the expression of miR-130a compared to control group of cells (P < 0.01). miR-130a was highly expressed in HK-2 cells (P < 0.001). Overexpression of miR-130a reversed LPS-induced apoptosis (P < 0.05), increased expression of inflammatory mediators and decreased cell viability (P < 0.05), and miR-130a knockdown in HK-2 cells revealed to just the opposite effects upon treatment with LPS. Western blotting results showed that overexpression of miR-130a promoted the expression of Klotho and activated the PI3K/AKT pathway but inhibited Wnt and NF-κB pathways. CONCLUSIONS: These findings demonstrated that miR-130a promoted PI3K/AKT pathway but inhibited Wnt and NF-κB pathways through upregulation of Klotho. Furthermore, miR-130a protects against lipopolysaccharide-induced glomerular cell injury by upregulating Klotho expression.