MicroRNAs in kidney development and disease

Cerqueira, Débora M.; Tayeb, Maliha; Ho, Jacqueline

doi:10.1172/jci.insight.158277

Cited by 22 publications

(15 citation statements)

References 185 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MicroRNAs are critical regulators of gene expression in health and diseases, including renal pathogenesis. 10,12,13 Recent work has also implicated microRNAs in kidney transplantation. 21,24–26,46–48 Although those studies revealed the changes in microRNA expression suggesting their diagnostic potential, the role of microRNAs as a whole class of molecules in kidney transplantation was not clear.…”

Section: Discussionmentioning

confidence: 99%

“…In kidneys, microRNAs play important roles in renal physiology and the pathogenesis of kidney diseases. 10,12,13 Targeting micro-RNAs has been widely explored as a therapeutic strategy, [14][15][16] and microRNA-based drugs have entered clinical trials treating CKDs. [17][18][19][20] However, therapies targeting microRNAs in AKI or renal transplantation have not yet entered the clinical stage.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

miR-147 Represses NDUFA4, Inducing Mitochondrial Dysfunction and Tubular Damage in Cold Storage Kidney Transplantation

Zhu

Xiang

et al. 2023

JASN

View full text Add to dashboard Cite

Background Kidney injury due to cold storage–associated transplantation (CST) is a major factor determining the outcome of renal transplant, for which the role and regulation of microRNAs remain largely unclear. Methods The kidneys of proximal tubule Dicer (an enzyme for microRNA biogenesis) knockout mice and their wild-type littermates were subjected to CST to determine the function of microRNAs. Small RNA sequencing then profiled microRNA expression in mouse kidneys after CST. Anti–microRNA-147 (miR-147) and miR-147 mimic were used to examine the role of miR-147 in CST injury in mouse and renal tubular cell models. Results Knockout of Dicer from proximal tubules attenuated CST kidney injury in mice. RNA sequencing identified multiple microRNAs with differential expression in CST kidneys, among which miR-147 was induced consistently in mouse kidney transplants and in dysfunctional human kidney grafts. Anti–miR-147 protected against CST injury in mice and ameliorated mitochondrial dysfunction after ATP depletion injury in renal tubular cells in intro. Mechanistically, miR-147 was shown to target NDUFA4, a key component of the mitochondrial respiration complex. Silencing NDUFA4 aggravated renal tubular cell death, whereas overexpression of NDUFA4 prevented miR-147–induced cell death and mitochondrial dysfunction. Moreover, overexpression of NDUFA4 alleviated CST injury in mice. Conclusions microRNAs, as a class of molecules, are pathogenic in CST injury and graft dysfunction. Specifically, miR-147 induced during CST represses NDUFA4, leading to mitochondrial damage and renal tubular cell death. These results unveil miR-147 and NDUFA4 as new therapeutic targets in kidney transplantation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-147 Represses NDUFA4, Inducing Mitochondrial Dysfunction and Tubular Damage in Cold Storage Kidney Transplantation

Zhu

Xiang

et al. 2023

JASN

View full text Add to dashboard Cite

show abstract

“…The regulation of miRNA biogenesis occurs at multiple levels, including binding of transcription factors to enhance miRNA genes, DROSHA processing of pri-miRNA, DICER processing of pre-miRNA, RNA methylation, editing of miRNA precursors, adenylation, uridylation, RNA decay, and many other mechanisms. [ 13 , 14 ] Recently, super-enhancers have also emerged as a new class of regulatory elements to control miRNA biogenesis by increasing transcription and DROSHA/ DGCR8-mediated pri-miRNA processing. Combined with a broad H3K4me3 profile, super-enhancer activity shapes the expression patterns and functions of tissue-specific miRNA.…”

Section: Microrna Biogenesis Function and Mirna-target Interactionmentioning

confidence: 99%

Role of microRNAs in programmed cell death in renal diseases: A review

Zhang

Chen

et al. 2023

Medicine

View full text Add to dashboard Cite

MicroRNAs (miRNAs) regulate gene expression involving kidney morphogenesis and cell proliferation, apoptosis, differentiation, migration, invasion, immune evasion, and extracellular matrix remodeling. Programmed cell death (PCD) is mediated and regulated by specific genes and a wealth of miRNAs, which participate in various pathological processes. Dysregulation of miRNAs can disrupt renal development and induce the onset and progression of various renal diseases. An in-depth understanding of how miRNAs regulate renal development and diseases is indispensable to comprehending how they can be used in new diagnostic and therapeutic approaches. However, the mechanisms are still insufficiently investigated. Hence, we review the current roles of miRNA-related signaling pathways and recent advances in PCD research and aim to display the potential crosstalk between miRNAs and PCD. The prospects of miRNAs as novel biomarkers and therapeutic targets are also described, which might provide some novel ideas for further studies.

show abstract

“…Alternation of miRNA expression is associated with early onset and faster progression of various diseases. 8 The linkage between certain miRNA and renal damage has also been demonstrated. A highly upregulated expression of miRNA-21 was observed in renal ischemia-reperfusion injury 9 and gentamicin-induced AKI.…”

Section: Introductionmentioning

confidence: 99%

Integrative analysis of renal microRNA and mRNA to identify hub genes and pivotal pathways associated with cyclosporine-induced acute kidney injury in mice

Yang,

Wang,

et al. 2023

Hum Exp Toxicol

View full text Add to dashboard Cite

Cyclosporine (CsA) is an immunosuppressive agent that often causes acute kidney injury (AKI) in children. The specific mechanisms underlying CsA-induced AKI are currently unknown. This study used an integrated network analysis of microRNA (miRNA) and mRNA expression profiles, biochemical and pathological analyses to further investigate these potential mechanisms of CsA-induced AKI. Small RNA sequence analysis identified 25 differentially expressed miRNAs, RNA sequencing analysis identified 4,109 differentially expressed mRNAs. We obtained a total of 4,367 target genes from the 25 differentially expressed miRNAs based on three algorithms, including the Mirdb, Mirtarbase, and TargetScan. 971 target genes overlapped between the 4,367 target genes and 4,109 differentially expressed mRNAs were identified for further bioinformatics analysis. Finally, 30 hub genes and two main modules were recognized. Functional enrichment analysis of 30 hub genes indicated that inflammation and epithelial-mesenchymal transition (EMT) related genes were mainly concentrated together. Pathway analysis revealed that the PI3K-Akt signaling pathway plays an integral role in CsA-induced AKI. Network analysis identified 3 important miRNAs, mmu‐miR-17b‐5p, mmu-miR-19b-3p, and mmu-mir-423-5p that may further promote the development of inflammatory responses and EMT by mediating a complex network of factors. Our research provides a clearer understanding the molecular mechanism of this specific drug-induced AKI by CsA use, which is useful for discovering potential targets for gene therapies, and drug development in CsA-induced AKI.

show abstract

MicroRNAs in kidney development and disease

Cited by 22 publications

References 185 publications

miR-147 Represses NDUFA4, Inducing Mitochondrial Dysfunction and Tubular Damage in Cold Storage Kidney Transplantation

miR-147 Represses NDUFA4, Inducing Mitochondrial Dysfunction and Tubular Damage in Cold Storage Kidney Transplantation

Role of microRNAs in programmed cell death in renal diseases: A review

Integrative analysis of renal microRNA and mRNA to identify hub genes and pivotal pathways associated with cyclosporine-induced acute kidney injury in mice

Contact Info

Product

Resources

About