JiangyaTongluo decoction ameliorates tubulointerstitial fibrosis via regulating the SIRT1/PGC-1α/mitophagy axis in hypertensive nephropathy DOI Creative Commons
Yun Zhao, Jia Qi, Gaimei Hao

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 12, 2024

Introduction With the increasing prevalence of hypertension, incidence kidney diseases is also increasing, resulting in a serious public burden. Jiangya Tongluo decoction (JYTL), recognized prescription traditional Chinese medicine (TCM), commonly used to calm an overactive liver and reduce excess yang, while promoting blood flow alleviate obstructions meridians. Previous research has indicated that JYTL may help mitigate damage caused by hypertension; however, underlying mechanisms have not been thoroughly assessed. Methods First, amalgamation UPLC-QE/MS network pharmacology techniques was employed pinpoint potential active components, primary targets, crucial action treating hypertensive nephropathy (HN). Then, we spontaneous rats (SHRs) Wistar-Kyoto (WKYs) evaluate efficacy on HN with valsartan as positive reference. We conducted DCFH-DA fluorescence staining rat renal tissues detect level ROS. Western blotting immunohistochemistry were performed investigate further effect key targets signaling pathways. Results Through analysis, 189 ingredients 5 hub identified from JYTL. GSEA MitoCarta3.0 database PPI analysis revealed predominantly engages Sirt1-mitophagy pathway. Tanshinone iia, quercetin, adenosine are main for HN. In vivo validation showed could improve function, ameliorate tubulointerstitial fibrosis (TIF), mitochondrial function inhibiting ROS production regulating dynamics SHRs. treatment increase expression SIRT1, PGC-1α, Nrf1, TFAM, activate PINK1/Parkin-mediated mitophagy. Conclusion exert protective anti-fibrosis effects ameliorating SIRT1/PGC-1α-mitophagy

Language: Английский

Pharmacological approaches to enhance mitochondrial biogenesis: focus on PGC-1Α, AMPK, and SIRT1 in cellular health DOI

Ahmet Alperen Palabiyik,

Esra Palabıyık

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Feb. 28, 2025

Language: Английский

Citations

1
Chaihuang Yishen Granule ameliorates mitochondrial homeostasis by upregulating PRDX5/TFAM axis to inhibit renal fibrosis in CKD DOI

Linghui Xu,

Ruizhi Tan,

Jing‐Yi Lin

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156426 - 156426

Published: Jan. 1, 2025

Language: Английский

Citations

0
Integrin-Linked Kinase (ILK) Promotes Mitochondrial Dysfunction by Decreasing CPT1A Expression in a Folic Acid-Based Model of Kidney Disease DOI Open Access

Mariano de la Serna-Soto,

Laura Calleros,

María Martos-Elvira

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1861 - 1861

Published: Feb. 21, 2025

Integrin-linked kinase (ILK) is a key scaffolding protein between extracellular matrix and the cytoskeleton has been implicated previously in pathogenesis of renal damage. However, its involvement mitochondrial dysfunction remains to be elucidated. We studied role ILK downstream regulations damage mitochondria function both vivo vitro, using folic acid (FA)-induced kidney disease model. Wild type (WT) conditional-knockdown (cKD-ILK) mice were injected with single intraperitoneal dose FA after 15 days chronic progression. Human Kidney tubular epithelial cells (HK2) transfected specific siRNAs targeting ILK, glycogen synthase 3-β (GSK3β), or CCAAT/enhancer binding protein-β (C/EBPβ). The expressions activities GSK3β, C/EBPβ, oxidative phosphorylation enzymes, membrane potential assessed. Additionally, expression markers for fibrosis fibronectin (FN) collagen 1 (COL1A1), autophagy p62 cytosolic light chain 3 (LC3B) isoforms II I, homeostasis marker carnitine palmitoyl-transferase 1A (CPT1A) evaluated immunoblotting, RT-qPCR, immunofluorescence, colorimetric assays. upregulated expression, leading decrease GSK3β activity, increased fibrosis, produced dysfunction, vitro. These alterations fully partially reversed upon depletion, mitigating FA-induced signaling axis composed by C/EBPβ regulated CPT1A transcription as limiting factor FA-based impaired activity. highlight therapeutical target preserving injury.

Language: Английский

Citations

0
Role of peroxisomes in the pathogenesis and therapy of renal fibrosis DOI
Dan Zhang,

Yang-He Zhang,

Bin Liu

et al.

Metabolism, Journal Year: 2025, Volume and Issue: 166, P. 156173 - 156173

Published: Feb. 22, 2025

Language: Английский

Citations

0
Cordycepin Ameliorates Renal Interstitial Fibrosis by Inhibiting Drp1-Mediated Mitochondrial Fission DOI Creative Commons
Yingxue Sun, Shi Jin, Jun Chen

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 1271 - 1287

Published: Feb. 1, 2025

This study aimed to investigate the mechanisms and specific targets of cordycepin in treatment renal fibrosis using a unilateral ischemia-reperfusion (UIR) model. A UIR mouse model was established, followed by intraperitoneal injections Mdivi-1. Masson's trichrome staining PAS were used identify tubulointerstitial assess degree injury. Fibrosis markers mitochondrial dynamics-related proteins evaluated Western blotting, while differential gene expression pathway enrichment analyzed RNA-seq. Molecular docking, molecular dynamics simulations surface plasmon resonance conducted validate binding sites on target protein Drp1. Immunofluorescence vitro experiments further elucidated therapeutic mechanism cordycepin. In vivo showed that injection significantly reduced inflammation fibrosis, lowered serum creatinine levels, decreased collagen deposition. Transcriptome analysis revealed downregulated fission upregulated fusion pathway. blotting levels α-SMA FN, as well downregulation Drp1, MFF, Fis1, upregulation OPA1 Mfn2. vitro, inhibited TGF-β-induced injury NRK-52E cells, reducing Drp1 IL-6 secretion. Crosstalk confirmed crucial for anti-fibrotic effects suppressing fibroblast activation. Cordycepin ameliorates targeting inhibit injured tubular epithelial secretion inhibiting

Language: Английский

Citations

0
Inhibition of METTL3 promotes mesangial cell mitophagy and attenuates glomerular damage by alleviating FOSL1 m6A modifications via IGF2BP2-dependent mechanisms DOI
Tao Liu,

Xing Xing Zhuang,

Xiao Zhu

et al.

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116867 - 116867

Published: March 1, 2025

Language: Английский

Citations

0
Targeting autophagy in autoimmune glomerular diseases DOI
Claudio Ponticelli,

Moroni Gabriella

Journal of Nephrology, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Language: Английский

Citations

0
Combining mitochondrial proteomes and Mendelian randomization to identify novel therapeutic targets for diabetic nephropathy DOI Creative Commons
Yang Liu, Rong Wu, Zhenlei Zhou

et al.

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

Published: March 24, 2025

Diabetic nephropathy (DN) is a common microvascular complication of diabetes. Mitochondrial dysfunction in the kidney caused by diabetes has previously been linked to pathogenesis DN. By mass spectrometry, we identified characteristic proteins DN from renal mitochondria mouse model. To identify core among them, Mendelian randomization (MR) analysis, microarray data validation, and drug-target interaction analysis were employed. MR found that 189 candidate targets had causal link with risk factors (estimated glomerular filtration rate (eGFR), urinary albumin excretion, serum creatinine). After systematic validated SLC25A16, CTNND1, C2CD2L, ALDH3A2, NEU1, APEH, CORO1A, NUDT19, NDUFA4L2 are promising druggability This study suggests feasibility using for drug target screening, provides potential insights into mitochondrial research, which may contribute further exploration.

Language: Английский

Citations

0
REST contributes to renal fibrosis through inducing mitochondrial energy metabolism imbalance in tubular epithelial cells DOI Creative Commons
Yu Yang, Shuiqin Gong, Chun Zhou

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 8, 2025

Renal fibrosis represents the final common pathological manifestation of chronic kidney disease (CKD), yet underlying mechanism remains elusive, and there is still a lack effective targeted therapeutic strategy. Although previous research indicated that repressor element 1-silencing transcription factor (REST) contributed to acute injury (AKI) in renal tubular epithelial cells (RTECs), its specific contribution associated mechanisms largely unexplored. biopsies from CKD patients were collected evaluate expression REST. Kidney-specific Rest conditional knockout (Cdh16-Cre/Restflox/flox) mice generated employed unilateral ureter obstruction (UUO) models investigate role REST fibrosis. RNA sequencing was performed elucidate mechanism. Mitochondrial function evaluated by transmission electron microscopy (TEM), reactive oxygen species (ROS), consumption rates (OCR), extracellular acidifcation rate (ECAR) adenosine triphosphate (ATP). The severity assessed through Western blot, immunofluorescent staining immumohistochemical staining. Bioinformatic prediction, dual luciferase reporter gene assay, point mutation chromatin immunoprecipitation (ChIP) assay utilized clarify molecular significantly up-regulated tissues patients, UUO-induced fibrotic mouse TGF-β1-incubated RTECs. Notably, kidney-specific prominently alleviated improving mitochondrial energy metabolism restoring fatty acid oxidation. Mechanically, disturbed repressing oxoglutarate dehydrogenase-like (OGDHL) via directly binding promotor region. Further, pharmacological inhibition using inhibitor, X5050, ameliorated progression both vitro vivo. Our explorations revealed upregulation disrupts transcriptionally suppressing OGDHL, which may act as promising target for

Language: Английский

Citations

0
Mechanism of Mitophagy to Protect Yak Kidney from Hypoxia-Induced Fibrosis Damage by Regulating Ferroptosis Pathway DOI Creative Commons
Xuefeng Bai,

Hongqin Lu,

Rui Ma

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 556 - 556

Published: April 9, 2025

Renal fibrosis is a critical pathological feature of various chronic kidney diseases, with hypoxia being recognized as an important factor in inducing fibrosis. Yaks have long inhabited high-altitude hypoxic environments and do not exhibit fibrotic damage under hypoxia. However, the underlying protective mechanisms remain unclear. This study compared renal tissue structure collagen volume between low-altitude cattle yaks, revealing that yaks possess significantly higher number tubules than cattle, though showed no significant difference. Under treatment, we observed induced but did show effect suggesting adaptation may anti-fibrotic effect. Further investigation demonstrated upregulation P-AMPK/AMPK, Parkin, PINK1, LC3Ⅱ/Ⅰ, BECN1, alongside downregulation P-mTOR/mTOR yak kidneys. Additionally, hypoxia-induced tubular epithelial cells (RTECs) increased expression mitophagy-related proteins, mitochondrial membrane depolarization, lysosomes, indicating induces mitophagy. By regulating mitophagy pathway through drugs, found hypoxia, activation upregulated E-cadherin protein while downregulating Vimentin, α-SMA, Collagen I, Fibronectin. Simultaneously, there was increase SLC7A11, GPX4, GSH levels, decrease ROS, MDA, Fe2⁺ accumulation. Inhibition produced opposite effects on cellular markers. studies identified ferroptosis key mechanism promoting Moreover, models, reduced accumulation Fe2⁺, thereby alleviating ferroptosis-induced These findings suggest protects from by activating to inhibit pathway.

Language: Английский

Citations

0