The role of non-coding RNA in lupus nephritis

Liang, Hanzhi; Liu, Qinghua

doi:10.1007/s13577-023-00883-w

Cited by 6 publications

(6 citation statements)

References 117 publications

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“…Nevertheless, our grasp of the nexus between LN and lncRNAs remains circumscribed [30]. Emerging evidentiary support postulates that differentially expressed lncRNAs (DELs) contribute to LN pathogenesis, in uencing organ impairment and clinical parameters [31,32]. A study by Zhang et al revealed a speci c lncRNA termed NEAT1, identi ed as an early responder gene to lipopolysaccharide (LPS) stimulation [28].…”

Section: Discussionmentioning

confidence: 99%

Unveiling Urinary Biomarkers, Crucial Genes, and Immune Infiltration in Lupus Nephritis Patients

Zeng,

Xie,

et al. 2023

Preprint

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Background This study was conducted to investigate the expression patterns and biological roles of urinary long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in individuals diagnosed with lupus nephritis (LN). Methods The study cohort comprised six participants: three with systemic lupus erythematosus (SLE) involving LN, three with SLE without LN, and three healthy controls (CON). Microarray technology was employed to analyze urinary mRNAs and lncRNAs, thereby exploring alterations in overall RNA expression. Functional insights into dysregulated differentially expressed mRNAs (DEMs) associated with LN were derived through gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). Furthermore, the construction of a protein-protein interaction (PPI) network was accomplished using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The identification of immune-related cell types was facilitated by Single-sample Gene Set Enrichment Analysis (ssGSEA). To predict potential drug candidates based on differentially expressed genes (DEGs), Connectivity Map (CMap) analysis was conducted. Results Within the urine samples of SLE patients, a total of 247 mRNAs and 602 lncRNAs exhibited differential expression relative to the control group. Among these, 83 down-regulated and 141 up-regulated DEMs were specifically discerned in patients with LN. GO analysis of the network highlighted enrichment in processes such as transcriptional regulation, intrinsic apoptotic signaling pathways in response to DNA damage, and the regulation of mitophagy. KEGG pathway analysis primarily revealed enrichment in protein processing within the endoplasmic reticulum, apoptosis, and the P53 signaling pathway. Co-expression and PPI network analysis suggested that nodes with higher degrees of connectivity were concentrated in pathways related to apoptosis and autophagy. An assessment of immune infiltration unveiled a correlation between activated B cells and CD56dim natural killer (NK) cells with LN pathogenesis. The prediction of drugs implicated inhibition of mechanistic Aurora kinase A (AURKA) as a primary targeted intervention. The molecular docking process confirmed the robust binding activity of hub genes' components. Conclusion This study has illuminated the distinct expression profiles of urinary long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in lupus nephritis (LN) patients. These profiles, particularly in the context of apoptosis, autophagy, and immune cell involvement, provide valuable insights into LN's underlying mechanisms. The identification of potential therapeutic targets, such as mechanistic AURKA, offers promising directions for future interventions in LN management.

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Section: Discussionmentioning

confidence: 99%

Unveiling Urinary Biomarkers, Crucial Genes, and Immune Infiltration in Lupus Nephritis Patients

Zeng,

Xie,

et al. 2023

Preprint

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“…lncRNAs and circRNAs can wipe up or sponge the effect of miRs, and consequently affect the downstream signaling pathways. Many authors have reviewed the evidence from animal and human studies and suggested that the expression of miRs [ 182 , 183 ] and lncRNAs [ 184 , 185 ] are altered in LN and can become new biomarkers for the disease. Ahmed et al [ 186 ] disclosed an interesting finding that miR-132 and its corresponding lncRNA, SOX2, were reciprocally expressed in the sera of LN patients.…”

Section: Potential Novel Therapeutic Strategy For Ln In Futurementioning

confidence: 99%

Decipher the Immunopathological Mechanisms and Set Up Potential Therapeutic Strategies for Patients with Lupus Nephritis

Tsai

Shen

et al. 2023

IJMS

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Lupus nephritis (LN) is one of the most severe complications in patients with systemic lupus erythematosus (SLE). Traditionally, LN is regarded as an immune complex (IC) deposition disease led by dsDNA–anti-dsDNA-complement interactions in the subendothelial and/or subepithelial basement membrane of glomeruli to cause inflammation. The activated complements in the IC act as chemoattractants to chemically attract both innate and adaptive immune cells to the kidney tissues, causing inflammatory reactions. However, recent investigations have unveiled that not only the infiltrating immune-related cells, but resident kidney cells, including glomerular mesangial cells, podocytes, macrophage-like cells, tubular epithelial cells and endothelial cells, may also actively participate in the inflammatory and immunological reactions in the kidney. Furthermore, the adaptive immune cells that are infiltrated are genetically restricted to autoimmune predilection. The autoantibodies commonly found in SLE, including anti-dsDNA, are cross-reacting with not only a broad spectrum of chromatin substances, but also extracellular matrix components, including α-actinin, annexin II, laminin, collagen III and IV, and heparan sulfate proteoglycan. Besides, the glycosylation on the Fab portion of IgG anti-dsDNA antibodies can also affect the pathogenic properties of the autoantibodies in that α-2,6-sialylation alleviates, whereas fucosylation aggravates their nephritogenic activity. Some of the coexisting autoantibodies, including anti-cardiolipin, anti-C1q, anti-ribosomal P autoantibodies, may also enhance the pathogenic role of anti-dsDNA antibodies. In clinical practice, the identification of useful biomarkers for diagnosing, monitoring, and following up on LN is quite important for its treatments. The development of a more specific therapeutic strategy to target the pathogenic factors of LN is also critical. We will discuss these issues in detail in the present article.

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“…In particular, microglia are important for removing damaged cells during membrane PS externalization and apoptosis [106,131,145,277,278,298,308,[324][325][326][327]]. Yet, microglia can lead to the generation of oxidative stress through the production of ROS [8,165,167,246,250,[328][329][330][331], which can require modulation by non-coding RNAs [251,[332][333][334][335][336], Wnt signaling [27,28,106,115,276,[337][338][339], and trophic factor pathways with erythropoietin (EPO) [27,[340][341][342][343][344][345][346]. In other scenarios, microglial cells can be helpful for protection during amyotrophic lateral sclerosis [347], remove brain amyloid [348,349], and preserve cholesterol homeostasis with autophagy …”

Section: Cellular Mechanisms Of Oxidative Stress Energy Metabolism An...mentioning

confidence: 99%

Section: Non-coding Rnas Micrornas and Circular Rnas In Metabolic Dis...mentioning

confidence: 99%

“…CircRNAs consist of non-coding RNAs of approximately 100 nucleotides [100,142,152,313,316,329,[333][334][335][336]414,419,432,[440][441][442][443][444][445]. First identified as having a circular structure, circRNAs use covalent bonds to maintain a circular nature, contain both cis and trans regulation, oversee the expression of genes through the sponging of miRNAs [335,[446][447][448], and can have value as biomarkers [329,335,429,432,436,449]. In vascular and metabolic disease, atherosclerosis may be prevented through circular antisense non-coding RNA in the INK4 locus (circANRIL) in vascular smooth muscle cells and macrophages by blocking exonuclease-mediated pre-ribosomal RNA generation and cell proliferation [450].…”

Section: Non-coding Rnas Micrornas and Circular Rnas In Metabolic Dis...mentioning

confidence: 99%

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Cornerstone Cellular Pathways for Metabolic Disorders and Diabetes Mellitus: Non-Coding RNAs, Wnt Signaling, and AMPK

Maiese

2023

Cells

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Metabolic disorders and diabetes (DM) impact more than five hundred million individuals throughout the world and are insidious in onset, chronic in nature, and yield significant disability and death. Current therapies that address nutritional status, weight management, and pharmacological options may delay disability but cannot alter disease course or functional organ loss, such as dementia and degeneration of systemic bodily functions. Underlying these challenges are the onset of aging disorders associated with increased lifespan, telomere dysfunction, and oxidative stress generation that lead to multi-system dysfunction. These significant hurdles point to the urgent need to address underlying disease mechanisms with innovative applications. New treatment strategies involve non-coding RNA pathways with microRNAs (miRNAs) and circular ribonucleic acids (circRNAs), Wnt signaling, and Wnt1 inducible signaling pathway protein 1 (WISP1) that are dependent upon programmed cell death pathways, cellular metabolic pathways with AMP-activated protein kinase (AMPK) and nicotinamide, and growth factor applications. Non-coding RNAs, Wnt signaling, and AMPK are cornerstone mechanisms for overseeing complex metabolic pathways that offer innovative treatment avenues for metabolic disease and DM but will necessitate continued appreciation of the ability of each of these cellular mechanisms to independently and in unison influence clinical outcome.

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The role of non-coding RNA in lupus nephritis

Cited by 6 publications

References 117 publications

Unveiling Urinary Biomarkers, Crucial Genes, and Immune Infiltration in Lupus Nephritis Patients

Unveiling Urinary Biomarkers, Crucial Genes, and Immune Infiltration in Lupus Nephritis Patients

Decipher the Immunopathological Mechanisms and Set Up Potential Therapeutic Strategies for Patients with Lupus Nephritis

Cornerstone Cellular Pathways for Metabolic Disorders and Diabetes Mellitus: Non-Coding RNAs, Wnt Signaling, and AMPK

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