Extracellular Vesicle MicroRNA in the Kidney DOI
Sekyung Oh, Chang Min Lee, Sang‐Ho Kwon

et al.

Comprehensive physiology, Journal Year: 2023, Volume and Issue: 13(3), P. 4833 - 4850

Published: June 26, 2023

Abstract Most cells in our body release membrane‐bound, nano‐sized particles into the extracellular milieu through cellular metabolic processes. Various types of macromolecules, reflecting physiological and pathological status producing cells, are packaged such so‐called vesicles (EVs), which can travel over a distance to target thereby transmitting donor cell information. The short, noncoding ribonucleic acid (RNA) called microRNA (miRNA) takes crucial part EV‐resident macromolecules. Notably, EVs transferring miRNAs induce alterations gene expression profiles recipient genetically instructed, base‐pairing interaction between their messenger RNAs (mRNAs), resulting either nucleolytic decay or translational halt engaged mRNAs. As other fluids, released urine, termed urinary (uEVs), carry specific sets miRNA molecules, indicate normal diseased states kidney, principal source uEVs. Studies have therefore been directed elucidate contents biological roles uEVs moreover utilize regulatory properties cargos ameliorating kidney diseases delivery via engineered EVs. We here review fundamental principles biology as well current understanding applications EV‐loaded kidney. further discuss limitations contemporary research approaches, suggesting future directions overcome difficulties advance both basic clinical treating diseases. © 2023 American Physiological Society. Compr Physiol 13:4833‐4850, 2023.

Language: Английский

Hydrogel-exosome system in tissue engineering: A promising therapeutic strategy DOI Creative Commons

Ming‐Hui Fan,

Jin-Kui Pi,

Chen‐Yu Zou

et al.

Bioactive Materials, Journal Year: 2024, Volume and Issue: 38, P. 1 - 30

Published: April 23, 2024

Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for "cell-free therapy" clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, physical properties akin to biological tissues, also found extensive utility engineering regenerative repair. The synergistic combination of hydrogels holds the potential not only enhance efficiency but collaboratively advance repair process. This review has summarized advancements made over past decade research hydrogel-exosome systems regenerating various tissues including skin, bone, cartilage, nerves tendons, with focus on methods encapsulating releasing within hydrogels. It critically examined gaps limitations current research, whilst proposed future directions applications this innovative approach.

Language: Английский

Citations

22
Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases DOI Open Access
Luis Alberto Bravo-Vázquez, Sujay Paul,

Miriam Guadalupe Colín-Jurado

et al.

Genes, Journal Year: 2024, Volume and Issue: 15(1), P. 123 - 123

Published: Jan. 19, 2024

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

Language: Английский

Citations

8
The modulatory effects of large and small extracellular vesicles from normal human urine on calcium oxalate crystallization, growth, aggregation, adhesion on renal cells, and invasion through extracellular matrix: An in vitro study DOI Creative Commons

Sudarat Hadpech,

Sakdithep Chaiyarit,

Somsakul Phuangkham

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116393 - 116393

Published: March 11, 2024

Urinary extracellular vesicles (uEVs) play important roles in physiologic condition and various renal/urological disorders. However, their kidney stone disease remain unclear. This study aimed to examine modulatory effects of large small uEVs derived from normal human urine on calcium oxalate (CaOx) crystals (the main component stones). After isolation, uEVs, total urinary proteins (TUPs) with equal (protein equivalent) concentration were added into crystal assays compare the control (without or TUPs). TUPs strongly inhibited CaOx crystallization, growth, aggregation crystal-cell adhesion. Large had lesser degree inhibition against growth adhesion, comparable compared TUPs. Small inhibitory as for all these assays. slightly promoted invasion through matrix, whereas did not affect this. Matching reported six datasets those modulator (StoneMod) database revealed that contained 18 known modulators (mainly inhibitors). These findings suggest serve inhibitors prevent healthy individuals formation.

Language: Английский

Citations

5
Depression of LncRNA DANCR alleviates tubular injury in diabetic nephropathy by regulating KLF5 through sponge miR-214-5p DOI Creative Commons

Y. Kuang,

Juan Yang,

Meimei Sun

et al.

BMC Nephrology, Journal Year: 2024, Volume and Issue: 25(1)

Published: April 12, 2024

Abstract Objective Diabetic nephropathy (DN) manifests a critical aspect in the form of renal tubular injury. The current research aimed to determine function and mechanism long non-coding ribonucleic acid (LncRNA) differentiation antagonising non-protein coding RNA (DANCR), with focus on its impact Methods Quantitative reverse transcription polymerase chain reaction was employed analyze levels DANCR serum patients DN or human proximal epithelial cells (human kidney 2 [HK2]). diagnostic significance assessed using receiver operating characteristic curve. A model established by inducing HK-2 high glucose (HG). Cell proliferation, apoptosis, inflammatory factors, reactive oxygen species (ROS), malondialdehyde (MDA) were detected Counting Kit − 8, flow cytometry, enzyme-linked immunosorbent assay. interaction between microRNA (miR)-214-5p Krüppel-like factor 5 (KLF5) investigated immunoprecipitation dual-luciferase reporter assays. Results Elevated observed HG-inducted ( P < 0.05). effectively identified from type diabetes mellitus. Silencing protected against HG-induced injury restoring cell inhibiting reducing secretion factors oxidative stress production functions as sponge for miR-214-5p, mitigation silencing partially attenuated reduced miR-214-5p Additionally, KLF5 target miR-214-5p. Conclusion potential alleviation via miR-214-5p/KLF5 axis, following silencing, introduces novel perspective approach mitigating DN.

Language: Английский

Citations

5
Identification of novel snoRNA-based biomarkers for clear cell renal cell carcinoma from urine-derived extracellular vesicles DOI Creative Commons
Konrad Grützmann, Karsten Salomo, Alexander Krüger

et al.

Biology Direct, Journal Year: 2024, Volume and Issue: 19(1)

Published: May 13, 2024

Abstract Background Clear cell renal carcinoma (ccRCC) is the most common subtype of RCC with high rates metastasis. Targeted therapies such as tyrosine kinase and checkpoint inhibitors have improved treatment success, but therapy-related side effects tumor recurrence remain a challenge. As result, ccRCC still mortality rate. Early detection before metastasis has great potential to improve outcomes, no suitable biomarker specific for available so far. Therefore, molecular biomarkers derived from body fluids been investigated over past decade. Among them, RNAs urine-derived extracellular vesicles (EVs) are very promising. Methods RNA was extracted EVs cohort 78 subjects (54 patients, 24 urolithiasis controls). RNA-seq performed on discovery cohort, subset whole (47 ccRCC, 16 urolithiasis). Reads were then mapped genome, expression quantified based 100 nt long contiguous genomic regions. Cluster analysis differential region adjustment age gender. The candidate validated by qPCR in entire cohort. Receiver operating characteristic, area under curve odds ratios used evaluate diagnostic models. Results An initial cluster data showed separation subjects’ gender, not status. following analyses done, adjusting gender age. regions differentially expressed between patients mainly overlapped small nucleolar (snoRNAs). four snoRNAs ( SNORD99 , SNORD22 SNORD26 SNORA50C ) quantitative PCR. Confounder-adjusted regression models classify validation into tumor-free subjects. Corresponding accuracies ranged 0.654 0.744. Models combining multiple genes risk factors obesity hypertension performance an accuracy up 0.811 p = 0.0091). Conclusions Our study uncovered previously unrecognized snoRNA EVs, advancing search robust, easy-to-use screening method.

Language: Английский

Citations

5
Mitochondria-derived vesicles and their potential roles in kidney stone disease DOI Creative Commons

Sakdithep Chaiyarit,

Visith Thongboonkerd

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 2, 2023

Abstract Recent evidence has shown significant roles of mitochondria-derived vesicles (MDVs) in mitochondrial quality control (MQC) system. Under mild stress condition, MDVs are formed to carry the malfunctioned components, such as DNA (mtDNA), peptides, proteins and lipids, be eliminated restore normal structure functions. severe oxidative dynamics (fission/fusion) mitophagy predominantly activated rescue Additionally, generation can also triggered major MQC machinery cope with unhealthy mitochondria when is unsuccessful for eliminating damaged or fission/fusion fail recover This review summarizes current knowledge on discuss their physiologic pathophysiologic conditions. In addition, potential clinical relevance therapeutics diagnostics kidney stone disease (KSD) emphasized.

Language: Английский

Citations

12
Non-Coding RNAs in Kidney Stones DOI Creative Commons
Guilin Wang, Jun Mi,

Jiangtao Bai

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 213 - 213

Published: Feb. 11, 2024

Nephrolithiasis is a major public health concern associated with high morbidity and recurrence. Despite decades of research, the pathogenesis nephrolithiasis remains incompletely understood, effective prevention lacking. An increasing body evidence suggests that non-coding RNAs, especially microRNAs (miRNAs) long RNAs (lncRNAs), play role in stone formation stone-related kidney injury. MiRNAs have been studied quite extensively nephrolithiasis, plethora specific miRNAs implicated involving remarkable changes calcium metabolism, oxalate oxidative stress, cell–crystal adhesion, cellular autophagy, apoptosis, macrophage (Mp) polarization metabolism. Emerging potential for as novel diagnostic biomarkers nephrolithiasis. LncRNAs act competing endogenous (ceRNAs) to bind miRNAs, thereby modulating mRNA expression participate regulation physiological mechanisms stones. Small interfering (siRNAs) may provide approach treatment by treating related metabolic conditions cause Further investigation into these will generate insights renal injury might lead new strategies diagnosing this disease.

Language: Английский

Citations

4
miR-148b-5p regulates hypercalciuria and calcium-containing nephrolithiasis DOI Creative Commons
Wei Zhu,

Zhen Zhou,

Chengjie Wu

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Aug. 25, 2024

Calcium-containing stones represent the most common form of kidney calculi, frequently linked to idiopathic hypercalciuria, though their precise pathogenesis remains elusive. This research aimed elucidate molecular mechanisms involved by employing urinary exosomal microRNAs as proxies for renal tissue analysis. Elevated miR-148b-5p levels were observed in exosomes derived from patients with stones. Systemic administration rat models resulted heightened calcium excretion, whereas its inhibition reduced stone formation. RNA immunoprecipitation combined deep sequencing identified a suppressor calcitonin receptor (Calcr) expression, thereby promoting excretion and Mice deficient Calcr distal epithelial cells demonstrated elevated calcification. Mechanistically, regulated through circRNA-83536/miR-24-3p signaling pathway. Human samples corroborated these results. In summary, regulates formation calcium-containing via circRNA-83536/miR-24-3p/Calcr axis, presenting potential target novel therapeutic interventions prevent nephrolithiasis.

Language: Английский

Citations

4
Extracellular Vesicles in Calcium Oxalate Nephrolithiasis: Emerging Biomarkers and Therapeutic Potential DOI Creative Commons
Zhu Wang,

Xu Changzhi,

Qiong Deng

et al.

Advanced NanoBiomed Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

Kidney stone ranks as one of the most prevalent disorders in urology department, causing substantial personal suffering and healthcare costs globally. However, prediction, early diagnosis, treatment kidney disease are still limited. Extracellular vesicles (EVs), loaded with nucleic acids, proteins, metabolites, lipids, released by a wide variety cell types have potential biomarkers for disease. Meanwhile, some natural EVs derived from plants animals been evidenced to effects on elimination calcium oxalate crystals. More importantly, recent explorations elucidated multifaceted role therapeutic applications. These engineered can be RNAs, oligonucleotides, peptides, small molecules; this approach has shown great promise targeted drug delivery presents solution challenges prevention treatment. This review focuses blood, urine, kidney, gut microbiota, urine bacteria, which contribute crystal elimination. The is significant, offering personalized options. it crucial assess moving EV‐based therapies laboratory settings clinical

Language: Английский

Citations

0
Exosome-mediated crosstalk between epithelial cells amplifies the cell injury cascade in CaOx stone formation DOI Creative Commons
Yuanyuan Yang, Senyuan Hong, Qing Wang

et al.

Journal of Biological Engineering, Journal Year: 2023, Volume and Issue: 17(1)

Published: Feb. 28, 2023

Abstract Background Calcium oxalate (CaOx) stone disease is found worldwide. To explore the role of exosomes as a mediator intercellular crosstalk during CaOx formation, we conducted this study, which may provide new insight into treatment and prevention stones. Methods Exosomes derived from HK2 cells with (EXO(S)) or without (EXO(C))CaOx crystal stimulation were cocultured normal tubular epithelial subcapsularly injected rat kidneys. Then, oxidative stress levels, MAPK signalling pathway osteogenic changes detected via qPCR, Western blotting, immunofluorescence immunohistochemical staining. In vivo fluorescence imaging exosome internalization assays showed absorption utilization exosomes. Results EXO(S) increased reactive oxygen species (ROS) level activated expression BMP2, OPN OCN MAPK/P-38 both in vitro. experiments that preinjection aggravated, while EXO(C) ameliorated, these effects. Crystal depositions significantly SD rats GAM when they preinjected EXO(S), effects could be reversed after EXO(C). Conclusion Our study revealed exosome-mediated accelerate formation stones by promoting cascade cells. Graphical stimulated crystals released more exosomal miR-223-3p S100A8 comparing These amplify pathway, finally led to Randall’s plaque.

Language: Английский

Citations

7