Elevated hsa‐miR‐590‐3p expression down‐regulates HMGB2 expression and contributes to the severity of IgA nephropathy

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.

Extracellular vesicles derived from patients with antibody-mediated rejection induce tubular senescence and endothelial to mesenchymal transition in renal cells

“…Furthermore, miR‐590‐3p plays a key role in cellular aging, cancer, 76 AKI, 77 correlated with severity of IgA nephropathy 78 and targeted genes associated with inflammasome (NLRP1/IL‐1β) and renal oxidative stress (NOX4) 79 . This target was upregulated in AAMR group compared with CAMR and even if no statistical significance was reached, it could represent a potential marker for differential diagnosis.…”

MicroRNA-Mediated Downregulation of HMGB2 Contributes to Cellular Senescence in Microvascular Endothelial Cells

“…Since it is important to maintain a sufficient intranuclear amount of HMGB2 protein for the proper function of HMGB2, the downregulation via miRNA can induce related disorders. miRNA-127 controls embryonic stem cell pluripotency via the HMGB2-OCT/SOX2 axis [56], and miR-590-3p contributes to the severity of IgA nephropathy via downregulation of HMGB2 in peripheral mononuclear cells [57]. The abnormal overexpression of miR-23b-5p promotes cardiac hypertrophy and dysfunction via HMGB2 [58], and aberrant expression of miR-127-5p impairs the function of granulosa cells via HMGB2 in premature ovarian insufficiency [59].…”

Pathogenic Role of MicroRNA Dysregulation in Podocytopathies

“…And Osamu et al suggested that glomerular miR-26a expression decreased significantly in both IgAN mice and patients, which was closely linked to the progression of podocyte injury in IgAN (Ichii et al, 2014). In addition, other studies have also reported the involvement of some other dysregulated miRNAs in IgAN, such as miR-223 (Bao et al, 2014a), miR-590-3p (Zhai et al, 2019), miR-133a/b (Jin et al, 2018), miR-320 (Li et al, 2018), miR-100-3p, miR-877-3p (Liang et al, 2016, miR-23b (Li H. et al, 2021), miR-214-3p (Li Y. et al, 2021, and miR-150-5p (Pawluczyk et al, 2021). IgAN appears to be a systemic disease in which the kidneys are damaged as innocent bystanders (Wyatt and Julian, 2013).…”