MicroRNA-26a-5p Restoration Ameliorates Unilateral Ureteral Obstruction-Induced Renal Fibrosis in Mice Through Modulating TGF-β Signaling

Chung, Y.; Huang, Gong-Kai; Kang, Chih-Hsiung; Cheng, Yufang; Kao, Ying‐Hsien; Chien, Yu-Yi

doi:10.1016/j.labinv.2023.100131

Cited by 7 publications

(5 citation statements)

References 48 publications

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“…Epigenetic therapies represent promising alternatives to slow down renal fibrosis progression as they can target pathways present in fibrotic niches, which refer to the microenvironments where scarring occurs [112]. Several ncRNAs, such as miR-29b [114], miR-122a [115], miR-21a-5p [116], lncRNA CRNDE as well as miR-29a-3p [117], and miR-26a-5p [118], have been shown to attenuate renal fibrosis. Therefore, they have the potential to be targeted through therapeutic approaches in order to treat renal fibrosis.…”

Section: Therapeutic Inferences Of Mirnas and Lncrnas In Renal Fibrosismentioning

confidence: 99%

“…Likewise, miR-26a-5p has been found to be downregulated in kidneys affected by fibrosis. Chung et al [118] reported that intravenous miR-26a-5p restoration in UUOoperated mice suppressed the expression of markers associated with EMT, particularly TGFβ1 and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and reduced inflammation. In addition, in vitro experiments on NRK-49F cells and a human tissue microarray with renal fibrosis confirmed miR-26a-5p restoration in renal fibrosis tissue has antifibrotic and anti-inflammatory effects, showing its potential for developing ncRNA therapeutic approaches [118].…”

Section: Therapeutic Inferences Of Mirnas and Lncrnas In Renal Fibrosismentioning

confidence: 99%

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Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases

Bravo-Vázquez,

Paul,

Colín-Jurado

et al. 2024

Genes

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MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two crucial classes of transcripts that belong to the major group of non-coding RNAs (ncRNAs). These RNA molecules have significant influence over diverse molecular processes due to their crucial role as regulators of gene expression. However, the dysregulated expression of these ncRNAs constitutes a fundamental factor in the etiology and progression of a wide variety of multifaceted human diseases, including kidney diseases. In this context, over the past years, compelling evidence has shown that miRNAs and lncRNAs could be prospective targets for the development of next-generation drugs against kidney diseases as they participate in a number of disease-associated processes, such as podocyte and nephron death, renal fibrosis, inflammation, transition from acute kidney injury to chronic kidney disease, renal vascular changes, sepsis, pyroptosis, and apoptosis. Hence, in this current review, we critically analyze the recent findings concerning the therapeutic inferences of miRNAs and lncRNAs in the pathophysiological context of kidney diseases. Additionally, with the aim of driving advances in the formulation of ncRNA-based drugs tailored for the management of kidney diseases, we discuss some of the key challenges and future prospects that should be addressed in forthcoming investigations.

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Section: Therapeutic Inferences Of Mirnas and Lncrnas In Renal Fibrosismentioning

confidence: 99%

Section: Therapeutic Inferences Of Mirnas and Lncrnas In Renal Fibrosismentioning

confidence: 99%

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases

Bravo-Vázquez,

Paul,

Colín-Jurado

et al. 2024

Genes

View full text Add to dashboard Cite

show abstract

“…MicroRNAs (miRNAs), single-stranded noncoding RNAs that can regulate target gene expression either by blocking mRNA translation or promoting mRNA degradation, impact expression of many kidney-related fibrotic proteins. MiR-26a specifically exerts antifibrotic effects and is downregulated in certain fibrotic diseases of the kidney, heart, and lungs [264]. Zheng et al induced tubulointerstitial fibrosis in mice using aldosterone and found increased CTGF in the kidney tissue [265].…”

Section: Rna-based Therapeuticsmentioning

confidence: 99%

Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets

Reiss,

Jacob,

Zubair

et al. 2024

JCM

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Chronic kidney disease (CKD) is a slowly progressive condition characterized by decreased kidney function, tubular injury, oxidative stress, and inflammation. CKD is a leading global health burden that is asymptomatic in early stages but can ultimately cause kidney failure. Its etiology is complex and involves dysregulated signaling pathways that lead to fibrosis. Transforming growth factor (TGF)-β is a central mediator in promoting transdifferentiation of polarized renal tubular epithelial cells into mesenchymal cells, resulting in irreversible kidney injury. While current therapies are limited, the search for more effective diagnostic and treatment modalities is intensive. Although biopsy with histology is the most accurate method of diagnosis and staging, imaging techniques such as diffusion-weighted magnetic resonance imaging and shear wave elastography ultrasound are less invasive ways to stage fibrosis. Current therapies such as renin-angiotensin blockers, mineralocorticoid receptor antagonists, and sodium/glucose cotransporter 2 inhibitors aim to delay progression. Newer antifibrotic agents that suppress the downstream inflammatory mediators involved in the fibrotic process are in clinical trials, and potential therapeutic targets that interfere with TGF-β signaling are being explored. Small interfering RNAs and stem cell-based therapeutics are also being evaluated. Further research and clinical studies are necessary in order to avoid dialysis and kidney transplantation.

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“…Renal interstitial fibrosis (RIF) caused by tubular atrophy and tubular epithelial cell injury is the main cause and common pathological process, leading to chronic renal failure and end-stage renal disease, and tubular epithelial cell injury is the key factor and central link of RIF [6]. Epithelial interstitial transformation (EMT) plays an important role in RIF [7], and its mechanism and influencing factors include the TGF-β1 pathway [8] and inflammatory factors such as NF-κB activation [9]. After the injury of renal tubular epithelial cells, a large number of pro-inflammatory factors are released and inflammatory cells are recruited, further aggravating kidney injury [10].…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV alleviates renal fibrosis by inhibiting renal tubular epithelial cell pyroptosis induced by urotensin II through regulating the cAMP/PKA signaling pathway

Zhang,

Liu,

et al. 2024

PLoS ONE

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Objective To explore the molecular mechanism of Astragaloside IV (AS-IV) in alleviating renal fibrosis by inhibiting Urotensin II-induced pyroptosis and epithelial-mesenchymal transition of renal tubular epithelial cells. Methods Forty SD rats were randomly divided into control group without operation: gavage with 5ml/kg/d water for injection and UUO model group: gavage with 5ml/kg/d water for injection; UUO+ AS-IV group (gavage with AS-IV 20mg/kg/d; and UUO+ losartan potassium group (gavage with losartan potassium 10.3mg/kg/d, with 10 rats in each group. After 2 weeks, Kidney pathology, serum Urotensin II, and cAMP concentration were detected, and the expressions of NLRP3, GSDMD-N, Caspase-1, and IL-1β were detected by immunohistochemistry. Rat renal tubular epithelial cells were cultured in vitro, and different concentrations of Urotensin II were used to intervene for 24h and 48h. Cell proliferation activity was detected using the CCK8 assay. Suitable concentrations of Urotensin II and intervention time were selected, and Urotensin II receptor antagonist (SB-611812), inhibitor of PKA(H-89), and AS-IV (15ug/ml) were simultaneously administered. After 24 hours, cells and cell supernatants from each group were collected. The cAMP concentration was detected using the ELISA kit, and the expression of PKA, α-SMA, FN, IL-1β, NLRP3, GSDMD-N, and Caspase-1 was detected using cell immunofluorescence, Western blotting, and RT-PCR. Results Renal tissue of UUO rats showed renal interstitial infiltration, tubule dilation and atrophy, renal interstitial collagen fiber hyperplasia, and serum Urotensin II and cAMP concentrations were significantly higher than those in the sham operation group (p <0.05). AS-IV and losartan potassium intervention could alleviate renal pathological changes, and decrease serum Urotensin II, cAMP concentration levels, and the expressions of NLRP3, GSDMD-N, Caspase-1, and IL-1β in renal tissues (p <0.05). Urotensin II at a concentration of 10−8 mol/L could lead to the decrease of cell proliferation, (p<0.05). Compared with the normal group, the cAMP level and the PKA expression were significantly increased (p<0.05). After intervention with AS-IV and Urotensin II receptor antagonist, the cAMP level and the expression of PKA were remarkably decreased (p<0.05). Compared with the normal group, the expression of IL-1β, NLRP3, GSDMD-N, and Caspase-1 in the Urotensin II group was increased (p<0.05), which decreased in the AS-IV and H-89 groups. Conclusion AS-IV can alleviate renal fibrosis by inhibiting Urotensin II-induced pyroptosis of renal tubular epithelial cells by regulating the cAMP/PKA signaling pathway.

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MicroRNA-26a-5p Restoration Ameliorates Unilateral Ureteral Obstruction-Induced Renal Fibrosis in Mice Through Modulating TGF-β Signaling

Cited by 7 publications

References 48 publications

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases

Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets

Astragaloside IV alleviates renal fibrosis by inhibiting renal tubular epithelial cell pyroptosis induced by urotensin II through regulating the cAMP/PKA signaling pathway

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