Abstract
Peripheral blood mononuclear cells (PBMCs) play important roles in the pathogenesis of IgA nephropathy (IgAN). Our study aimed to provide a deep understanding of IgAN and focused on the dysregulation of hsa‐miR‐590‐3p and its target gene HMGB2 in PBMCs. Three gene expression profile datasets (GSE14795, GSE73953 and GSE25590) were downloaded from the GEO database. The DEGs (differentially expressed genes)‐miRNA network that was associated with IgAN was constructed by Cytoscape, and HMGB2 and hsa‐miR‐590‐3p were selected for further exploration. The dual‐luciferase reporter system was utilized to verify their interaction. Then, the expression levels of HMGB2 and hsa‐miR‐590‐3p in PBMCs were detected by qPCR in another cohort, and the correlation of their expression levels with the clinical pathological manifestations and serum Gd‐IgA1(galactose‐deficient IgA1) levels was also investigated. HMGB2 was identified as the target gene of hsa‐miR‐590‐3p. Furtherly, the elderly patients had higher HMGB2 expression levels than the expression levels of the younger patients. As the serum creatinine, serum BUN levels increased, the expression of HMGB2 decreased; Besides, the HMGB2 expression was positively correlated with serum complement 3(C3) levels, and it also had a negative correlation with the diastolic blood pressure, but not reach statistical significance. What is more, both hsa‐miR‐590‐3p and HMGB2 expression had a slight correlation tendency with serum Gd‐IgA1 levels in the whole population. In conclusion, HMGB2, the target gene of hsa‐miR‐590‐3p, was identified to correlate with the severity of IgAN, and this provides more clues for the pathogenesis of IgAN.
Highlights
Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and is characterized by predominant IgA deposition in the mesangial area
The presence of galactose‐deficient IgA1(Gd‐IgA1) in the glomerular deposits of patients with IgAN has been proven by immunohistochemical staining using the galac‐ tose‐deficient IgA1‐specific monoclonal antibody KM55,7,8 which reinforces the important role that galactose‐deficient IgA1 plays in IgAN
After the validation of the decreased expression of HMGB2 in IgAN pa‐ tients, which was down‐regulated by the increased has‐miR‐590‐3p lev‐ els, we further explored their association with clinical findings and the pathological lesions in patients with IgAN
Summary
Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and is characterized by predominant IgA deposition in the mesangial area. The multihit pathogen‐ esis model of IgAN has been widely accepted,[3] which indicates that circulating galactose‐deficient IgA1 is the cause. The contribution of galactose‐deficient IgA1 to IgAN pathogenesis has been validated in many studies.[4-6]. Previous studies have shown that the aberrant deposition of gly‐ cosylated IgA1 in the renal mesangial area was from circulation.[9,10]. Previous studies have identified many key proteins that are involved in the O‐glycosylation of IgA1, including APRIL and BAFF, and all of these proteins were expressed in PBMCs,[13-15] in‐ dicating that PBMCs are a whole cell population and that further investigation is needed. Many differentially expressed miRNAs in several kinds of human samples were identified as bio‐ markers or participants in IgAN pathogenesis,[17-22] indicating the im‐ portant pathophysiological role of miRNAs in IgAN.
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