Abstract
BackgroundDiabetic 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 Psoralea corylifolia Linn. (PCL), which was used to treat a number of diseases. In this study, we aimed to investigate whether psoralen could alleviate DN using in vitro model.MethodsCell viability assay and immunofluorescence were used to evaluate the effect of 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.ResultsHG-induced toxicity of HK-2 cells was alleviated by 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.ConclusionThis 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.
Highlights
Diabetic nephropathy (DN) causes the vast proportion of excess mortality for patients with diabetes
Since HK-2 cells exposed to high glucose (HG) for 48 h showed moderate viability reduction (Fig. 1a), 30 mM glucose and 48 h exposure was used to establish a DN model in vitro
Consistent with data of apoptosis, the inhibitory effect of psoralen on apoptosis associated factors was inhibited in the presence of antagomir. All these results indicated that psoralen inhibited HG-induced apoptosis in HK-2 cells via upregulating miR-874
Summary
Diabetic nephropathy (DN) causes the vast proportion of excess mortality for patients with diabetes. Psoralen is the major active ingredient of Psoralea corylifolia Linn. (PCL), which was used to treat a number of diseases. Persistent albuminuria (> 0.3 g/day) in a patient with either diabetic type 1 or 2 is regarded as the major clinical characterization of DN [2, 3]. DN affects approximately 25% of patients with type II diabetes, which become a leading cause of endstage renal disease worldwide [4, 5]. It has been used to treat a number of diseases including leukoderma, psoriasis, osteoporosis and asthma [12]. Psoralen is the major active ingredient of PCL [13, 14], which exhibits multiple biological properties including antiinflammatory, anti-tumor, anti-vitiligo, anti-urticaria, and immunomodulatory activities [15, 16]. The beneficial effect of psoralen on DN is rarely studied
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