NR5A2 promotes epithelial-to-mesenchymal transition in renal fibrosis by targeting MMP25 transcription DOI Creative Commons
Xiao Wang, Guang Chen,

Weimin Shan

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 7, 2024

Abstract Epithelial-to-mesenchymal transition (EMT) is crucial for the progression of renal tubulointerstitial fibrosis, typically leading to end-stage failure. The role Nuclear receptor subfamily 5 group A member 2 (NR5A2) in fibrosis not yet fully understood. This research assessed NR5A2 expression human and mouse models with unilateral ureteral obstruction (UUO). We further investigated NR5A2's function TGF-β1-driven tubular EMT. Our findings demonstrated a significant elevation profibrogenic agents like collagen-I(Col-Ⅰ), alpha-smooth muscle actin (α-SMA), fibronectin (FN) UUO-induced model. Suppressing blocking it ML180 diminished TGF-β1-induced E-cadherin, α-SMA, Col-Ⅰ , FN HK2 cells. Functionally, boosted MMP25 cells after TGF-β1 activation. Luciferase Chromatin Immunoprecipitation (ChIP) assays verified attachment distinct motif on promoter, initiating transcription. Crucially, silencing countered NR5A2-induced factors following These insights reveal that orchestrates TGF-β1-prompted EMT via MMP25, highlighting novel avenue curbing fibrosis.

Language: Английский

Depleting profibrotic macrophages using bioactivated in vivo assembly peptides ameliorates kidney fibrosis DOI
Qing Ouyang, Chao Wang,

Tian Sang

et al.

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(8), P. 826 - 841

Published: June 13, 2024

Language: Английский

Citations

7
Increased NPM1 inhibit ferroptosis and aggravate renal fibrosis via Nrf2 pathway in chronic kidney disease DOI Creative Commons

Wenjing Fu,

Mingyu Zhang, Yilin Meng

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1871(1), P. 167551 - 167551

Published: Oct. 20, 2024

Language: Английский

Citations

3
Editorial for “Evaluating the Potential of Quantitative Susceptibility Mapping for Detecting Iron Deposition of Renal Fibrosis in a Rabbit Model” DOI Open Access
Alexey Dimov, Martin R. Prince

Journal of Magnetic Resonance Imaging, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Journal of Magnetic Resonance ImagingEarly View Editorial for "Evaluating the Potential Quantitative Susceptibility Mapping Detecting Iron Deposition Renal Fibrosis in a Rabbit Model" Alexey V. Dimov PhD, Corresponding Author PhD [email protected] orcid.org/0000-0003-0460-6635 Department Radiology, Weill Cornell Medicine, New York, USASearch more papers by this authorMartin R. Prince MD, Martin orcid.org/0000-0002-9883-0584 author First published: 17 February 2025 https://doi.org/10.1002/jmri.29729 Level Evidence: 5 Technical Efficacy: Stage 2 Read full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare text full-text accessPlease review our Terms and Conditions Use check box below share version article.I have read accept Wiley Online Library UseShareable LinkUse link article with your friends colleagues. Learn more.Copy URL Share linkShare onEmailFacebookxLinkedInRedditWechat No abstract is available article. References 1Kovesdy CP. Epidemiology chronic kidney disease: An update 2022. Kidney Int Suppl 2022; 12(1): 7-11. https://doi.org/10.1016/j.kisu.2021.11.003. 10.1016/j.kisu.2021.11.003 Web Science®Google Scholar 2Huang R, Fu P, Ma L. fibrosis: From mechanisms therapeutic medicines. Signal Transduct Target Ther 2023; 8:129. https://doi.org/10.1038/s41392-023-01379-7. 10.1038/s41392-023-01379-7 CASPubMedGoogle 3Klinkhammer BM, Boor P. Emerging diagnostic strategies. Mol Aspects Med 93:101206. https://doi.org/10.1016/j.mam.2023.101206. 10.1016/j.mam.2023.101206 4Morrell GR, Zhang JL, Lee VS. resonance imaging fibrotic kidney. J Am Soc Nephrol 2017; 28(9): 2564-2570. https://doi.org/10.1681/ASN.2016101089. 10.1681/ASN.2016101089 CASPubMedWeb 5Friedli I, Crowe LA, Berchtold L, et al. magnetic index renal fibrosis assessment: A comparison between diffusion-weighted T1 mapping histological validation. Sci Rep 2016; 6:30088. https://doi.org/10.1038/srep30088. 10.1038/srep30088 6Zhang JG, Xing ZY, Zha TT, Longitudinal assessment rabbit induced unilateral ureteral obstruction using two-dimensional susceptibility weighted imaging. Magn Reson Imaging 2018; 47(6): 1572-1577. https://doi.org/10.1002/jmri.25915. 10.1002/jmri.25915 PubMedWeb 7Zha T, Z, Pan Evaluating potential quantitative detecting iron deposition model. 2025. https://doi.org/10.1002/jmri.29722. 10.1002/jmri.29722 PubMedGoogle Early ViewOnline Version Record before inclusion an issue ReferencesRelatedInformation

Language: Английский

Citations

0
Noninvasive grading of renal interstitial fibrosis and prediction of annual renal function loss in chronic kidney disease: the optimal solution of seven MR diffusion models DOI Creative Commons

Guanjie Yuan,

Zhouyan Liao,

Ping Liang

et al.

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: March 25, 2025

To explore the optimal choice of seven diffusion models (DWI, IVIM, DKI, CTRW, FROC, SEM, and sADC) to assess renal interstitial fibrosis (IF) annual function loss in chronic kidney disease (CKD). One hundred thirty-three CKD patients 30 controls underwent multi-b sequence scans. Patients were divided into training, testing, temporal external validation sets. Least absolute shrinkage selection operator regression logistic used select metrics for distinguishing mild from moderate-to-severe IF. The performances imaging, clinical, combined compared. A linear mixed-effects model calculated estimated glomerular filtration rate (eGFR) slope, multiple assessed association between 1-3-year eGFR slopes. sets had 75, 30, 28 patients, respectively. incorporating cortical fIVIM, MKDKI was superior clinical combining 24-hour urinary protein all (net reclassification index [NRI] > 0, p < 0.05). Decision curve analysis showed provided greater net benefit across most thresholds. Fifty-two, 35, 16 completed 1-, 2-, 3-year follow-ups. After adjusting covariates, fIVIM correlated with 1-year slope (β = 30.600, 0.001), αSEM 2- slopes 44.859, 0.002; β 95.631, 0.019). provides a useful comprehensive tool grading IF, as potential biomarkers progression.

Language: Английский

Citations

0
Bioinformatics analysis and experimental validation of potential targets and pathways in chronic kidney disease associated with renal fibrosis DOI Creative Commons

Cui Huimin,

Zhao Yuxin,

Peng Wang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 2, 2025

Chronic kidney disease (CKD) has emerged as a major health problem worldwide. Previous studies have shown that specific miRNA expression profiles of patients with CKD are significantly changed. In this study, we aim to elucidate the role miRNAs potential biomarkers in progression by integrating bioinformatics analysis experimental validation, thereby providing medical evidence for prevention and treatment CKD. Bioinformatics was used identify targets pathways CKD-associated renal fibrosis through randomly obtaining microarray data related Gene Expression Omnibus (GEO) database according inclusion exclusion criteria, conducting pathway enrichment constructing protein-protein interaction (PPI) networks miRNA-mRNA network Cytoscape 3.8.0. vitro experiments were employed verify mechanism miR-223-3p human tubular epithelial cells (HK2) Quantitative real-time PCR assays, Western blot, Immunofluorescence Double luciferase reporter gene experiment. Multi-group one-way variance (ANOVA) Dunnett-t test uesd analyze results SPSS24.0. 10 up-regulated 11 down-regulated screened out. Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) first analysis. MiR-223-3p (logFC=-2.047, p = 0.002) one four hub miRNAs. Furthermore, observed reduction α-smooth muscle actin (α-SMA) (p 0.001) Collagen type I alpha 1 (Col1-a1) 0.023) levels upon overexpression, which aligned our predictions. This downregulation attributed inhibition nuclear factor kappa-B (NF-κB) translocation subsequent decrease secretion inflammatory cytokines, such interleukin-6 (IL-6) 0.005). Conversely, when CHUK further overexpressed, inhibitory effect on epithelial-mesenchymal transition (EMT) attenuated, confirming between CHUK. Our findings provide compelling acts suppressor EMT specifically targeting modulating PI3K/Akt pathway, holds great promise novel therapeutic target treatment. Additionally, study offers avenue development future interventions aimed at halting or reversing

Language: Английский

Citations

0
Diagnostic Approaches in Hypertension and Chronic Kidney Disease Renal Markers in Evaluation and Follow-Up of Hypertension and Classical and Modern Imaging Techniques in Evaluation of BP Disorders DOI
Michel Burnier,

William Rodriguez,

Menno Pruijm

et al.

Updates in hypertension and cardiovascular protection, Journal Year: 2025, Volume and Issue: unknown, P. 273 - 301

Published: Jan. 1, 2025

Language: Английский

Citations

0
Perturbed gut microbiota and serum metabolites are associated with progressive renal fibrosis DOI Creative Commons

Run-Xi Wang,

Hong-Bing Zhou, Jin Gao

et al.

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: April 28, 2025

Introduction The intricate pathogenesis of renal fibrosis necessitates identifying biomarkers at various stages to facilitate targeted therapeutic interventions, which would enhance patient survival rates and significantly improve prognosis. Methods We investigated the changes in gut microbiota serum metabolites during early, middle, late rats using 16S rDNA sequencing UPLC-QTOF/MS-based metabolomics. Results identified 5, 21, 14 potential microbial markers 19, 23, 31 metabolic MOD1, MOD2, MOD4 groups, respectively. Bifidobacterium was as a shared marker between MOD1 MOD2 groups; Prevotellaceae_NK3B31_group Bacteroides were groups. pathways arachidonic acid metabolism retinol found play significant role modulation 1, 2, 4 weeks. Notably, 8,9-EET 5(S)-HPETE within these emerged critical determinants influencing fibrosis. Discussion Our findings demonstrated that severity is associated with dysbiosis alterations metabolites.

Language: Английский

Citations

0
Cellular crosstalk in fibrosis: insights into macrophage and fibroblast dynamics DOI Creative Commons

Zachary S.C.S. Froom,

Neal I. Callaghan, Locke Davenport Huyer

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 110203 - 110203

Published: May 1, 2025

Language: Английский

Citations

0
Protective effects and mechanisms of cynaroside on renal fibrosis in mice with unilateral ureteral obstruction DOI Creative Commons

Ah Young Yang,

Jung-Yeon Kim,

Mi‐Gyeong Gwon

et al.

Redox Report, Journal Year: 2025, Volume and Issue: 30(1)

Published: May 5, 2025

Renal fibrosis is a key factor in the progression of chronic kidney disease (CKD), and current treatments remain inadequate. In this study, we investigated therapeutic effects cynaroside (Cyn), natural flavonoid, mouse model renal induced by unilateral ureteral obstruction. Cyn treatment significantly ameliorated tubular injury interstitial while improving function. Mechanistically, inhibited expression fibrosis-related proteins suppressed Smad2/3 phosphorylation. Additionally, reduced myofibroblast accumulation inhibiting epithelial-mesenchymal transition, as indicated increased E-cadherin decreased levels mesenchymal markers. also oxidative stress downregulating prooxidant enzyme NADPH oxidase 4 restoring antioxidant enzymes. Furthermore, attenuated ferroptosis regulating proteins, including acyl-CoA synthetase long-chain family member 4, transferrin receptor 1, glutathione peroxidase levels. alleviated endoplasmic reticulum stress, evidenced downregulation markers such glucose-regulated protein 78 activating transcription 6, inflammation, confirmed macrophage infiltration lower cytokine production. Overall, demonstrated broad protective against modulating ferroptosis, ER positioning it potential agent for CKD management.

Language: Английский

Citations

0
Role of Histone Modifications in Kidney Fibrosis DOI Creative Commons

Shengyu Pan,

Tianhui Yuan,

Yuqi Xia

et al.

Medicina, Journal Year: 2024, Volume and Issue: 60(6), P. 888 - 888

Published: May 28, 2024

Chronic kidney disease (CKD) is characterized by persistent dysfunction, ultimately resulting in end-stage renal (ESRD). Renal fibrosis a crucial pathological feature of CKD and ESRD. However, there no effective treatment for this condition. Despite the complex molecular mechanisms involved fibrosis, increasing evidence highlights role histone modification its regulation. The reversibility modifications offers promising avenues therapeutic strategies to block or reverse fibrosis. Therefore, comprehensive understanding regulatory implications may provide novel insights into more safer approaches. This review recent advances particularly methylation acetylation. aim explore potential as targets treating

Language: Английский

Citations

3