Abstract
BackgroundLong non-coding RNAs (lncRNAs) are widely reported to be involved in the development of human diseases. HLA complex P5 (HCP5) deregulation is associated with various diseases. However, the function of HCP5 in diabetic nephropathy (DN) is unclear.MethodsHuman glomerular mesangial cells (HGMCs) were treated with high glucose (HG) to establish DN cell models. The expression of HCP5, miR-93-5p and high mobility group AT-hook 2 (HMGA2) mRNA was detected using quantitative polymerase chain reaction (QPCR). Cell proliferation and cell apoptosis were assessed using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of apoptosis- and fibrosis-related proteins and HMGA2 protein was quantified by western blot. The release of pro-inflammatory factor was checked using enzyme-linked immunosorbent assay (ELISA). The predicted relationship between miR-93-5p and HCP5 or HMGA2 was verified using dual-luciferase reporter assay, pull-down assay or RNA immunoprecipitation (RIP) assay.ResultsThe expression of HCP5 and HMGA2 was enhanced, while the expression of miR-93-5p was declined in DN serum samples and HG-treated HGMCs. HCP5 knockdown or miR-93-5p restoration ameliorated HG-induced HGMC proliferation, fibrosis and inflammation. MiR-93-5p was a target of HCP5, and miR-93-5p inhibition reversed the effects caused by HCP5 knockdown. Moreover, HMGA2 was a target of miR-93-5p, and HMGA2 overexpression abolished the effects of miR-93-5p restoration. HCP5 knockdown inhibited the AKT/mTOR signaling pathway.ConclusionHCP5 was implicated in DN progression by modulating the miR-93-5p/HMGA2 axis, which provided new insights into the understanding of DN pathogenesis.
Highlights
Long non-coding RNAs are widely reported to be involved in the development of human diseases
The expression of HLA complex P5 (HCP5) was elevated, while the expression of miR-93-5p was declined in serum samples from diabetic nephropathy (DN) patients and high glucose (HG)-administered Human glomerular mesangial cells (HGMCs) We examined the expression of HCP5 and miR-93-5p in DN serum samples and DN cell models
The expression of miR-93-5p was notably decreased in serum samples from DN patients and HG-administered HGMCs compared to normal subjects and normal glucose (NG)-induced HGMCs, respectively (Fig. 1C and D)
Summary
Long non-coding RNAs (lncRNAs) are widely reported to be involved in the development of human diseases. HLA complex P5 (HCP5) deregulation is associated with various diseases. The function of HCP5 in diabetic nephropathy (DN) is unclear. Diabetic nephropathy (DN), which affects approximately one-third of diabetic patients, is the main cause of endstage renal failure, with increasing incidence [1]. Dysfunction of mesangial cells contributes to DN development, including mesangial cell excessive proliferation and fibrosis, caused by the accumulating of extracellular matrix (ECM) components, such as collagen type I, III, IV, and fibronectin [3, 4]. The pathogenesis of DN is complex, and the mechanism of mesangial cell dysfunction is not fully understood. It is necessary to explore new mechanisms to prevent the development of DN
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