Psoralen alleviates high glucose-induced HK-2 cell injury by inhibition of Smad 2 signaling via upregulation of microRNA 874

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background:</jats:bold> Diabetic nephropathy (DN) causes the vast proportion of excess mortality for patients with diabetes. Novel therapeutic approaches slowing down its incidence is still lacking. Psoralen is the major active ingredient of <jats:italic>Psoralea corylifolia Linn. </jats:italic>(PCL), which was used to treat a number of diseases. In this study, we aimed to investigate whether psoralen could alleviate DN using<jats:italic> in vitro</jats:italic> model. <jats:bold>Methods: </jats:bold>Cell viability assay and immunofluorescence were used to evaluate the effect of<jats:bold> </jats:bold>psoralen on high glucose (HG)-stimulated human kidney HK-2 cells (48 h). RT-qPCR was used to detect the expressions of miRNA in cells. Cell transfection, apoptosis assay, inflammatory cytokines detection and Western blot were further performed to explore the underlying molecular mechanisms.<jats:bold>Results: </jats:bold>HG-induced toxicity of HK-2 cells was alleviated by<jats:bold> </jats:bold>psoralen. Meanwhile, the secretion of inflammatory cytokines and extracellular matrix (ECM) accumulation induced by HG in HK-2 cells were also decreased by psoralen. In addition, the expression of miR-874 in HK-2 cells was significantly upregulated by psoralen. Western blot assays indicated that psoralen could reverse HG-induced increase of TLR-4/NF-κB and Smad2 via upregulation of miR-874.<jats:bold>Conclusion: </jats:bold>This study demonstrated that psoralen could significantly alleviate HG-induced HK-2 cell injury via upregulation of miR-874. In addition, HG-induced increase of TLR-4/NF-κB and Smad2 was revered by psoralen. Therefore, psoralen might serve as an agent for the treatment of DN.</jats:p>

Circulating miRNAs in Type 2 Diabetic Patients with and without Albuminuria in Malaysia

“…However, in contrast to our finding, downregulation of miR-874-3p was observed in the in vitro mouse podocytes model, leading to upregulation of its target toll-like receptor 4 resulting in overexpression of inflammatory cytokines such as interleukin-, tumour necrosis factor-α, and IL-1b [33]. Similar downregulation of miR-874-3p was shown in hyperglycaemia-treated human kidney-2 cells, which was reversed by administration of psoralen, leading to reduction in inflammatory cytokines and extracellular accumulation toll-like receptor 4/nuclear factor kappa beta and Smad2 signalling pathway [34]. Downregulation of miR-874-3p was also reported in non-DKD conditions, such as in oesophageal squamous cell carcinoma tissues and cell lines, implicating signal transducer and activator of transcription (STAT)-3 as its downstream target, affecting cell proliferation, migration, and invasion [35].…”