![]() Transferrin receptor 1 (TFRC or TfR1) is an IgA1 receptor required for erythropoiesis and nervous system development ( Levy et al., 1999), which has been implicated in IgAN pathogenesis ( Moura et al., 2001). ![]() Therefore, GMC behavior is essential to the prevention and treatment of IgAN. Autocrine and paracrine actions of histamine, serotonin, cytokines, interleukin, and cell growth factors produced by proliferating GMCs ( Abboud, 2012) disturb the balance between mesangial matrix secretion and degradation, causing matrix accumulation in the glomeruli, glomerulosclerosis, and tubular interstitial fibrosis ( Nogueira et al., 2017). Activation of these innate immune cells in response to macromolecular substances, immune complexes, or hypoxia has been associated with IgAN development. Glomerular mesangial cells (GMCs) are located between glomerular capillary loops, adjacent to endothelial cells ( Sakai and Kriz, 1987), and connected with the glomerular basement membrane (GBM), where they participate in glomerular filtration ( Kriz et al., 1990). The “Multi-Hits” theory explains the aspects of IgAN pathogenesis with successive events, such as mucosal immune abnormalities, chronic inflammation ( Novak et al., 2011), and complement activation ( Tortajada et al., 2019), but specific pathogenic mechanisms remain unclear. IgAN is characterized by proliferation of mesangial cells and deposition of IgA-dominated immune complexes in the mesangium. The common chronic glomerular disease, IgA nephropathy (IgAN), progresses to end-stage renal disease (ESRD) within 20–30 years of diagnosis for 30%–40% of patients, necessitating renal replacement therapy, such as kidney transplantation or dialysis ( Lai et al., 2016). TFRC is considered to have potential as a clinical therapeutic target. ![]() RCC1 and RPPH1 were found to be TFRC-bound RNA targets involved in cell proliferation.ĭiscussion: In conclusion, molecular TFRC targets were identified in HRMCs and TFRC found to regulate gene transcription and AS. Expression of TFRC-regulated genes potentially associated with IgAN, including CENPH, FOXM1, KIFC1, TOP2A, FABP4, ID1, KIF20A, ATF3, H19, IRF7, and H1-2, and with AS, CYGB, MCM7 and HNRNPH1, were investigated by RT-qPCR and iRIP-seq data analyzed to identify TFRC-bound RNA targets. Results: TFRC-regulated AS genes were enriched in mRNA splicing and DNA repair, consistent with global changes due to TFRC overexpression (TFRC-OE). The aim was to identify potential RNA targets of TFRC at transcriptional and alternative splicing (AS) levels. Methods: In this study, TFRC was overexpressed in human renal tubular mesangial cells (HRMCs) and RNA-sequencing (RNA-seq) and improved RNA immunoprecipitation sequencing (iRIP-seq) were performed. Molecular mechanisms by which TFRC affects IgAN development remain unclear. Transferrin receptor1 (TFRC), an IgA receptor, is a potential RNA binding protein (RBP) which regulates expression of genes positively associated with the cell cycle and proliferation and is involved in IgAN. Introduction: IgA nephropathy (IgAN) is the most common primary glomerular disease (PGD) which could progress to renal failure and is characterized by aberrant IgA immune complex deposition. ![]() ![]() 3Center for Genome Analysis, Wuhan Ruixing Biotechnology Co., Ltd., Wuhan, China.2Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology, Harbin, China.1Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.Jian-Si Li 1* Xiao Chen 2 Ailing Luo 3 Dong Chen 3 ![]()
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