Ferroptosis and renal fibrosis: mechanistic insights and emerging therapeutic targets DOI Creative Commons

Guangna Lyu,

Hui Liao, Rongshan Li

et al.

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

Published: May 6, 2025

Ferroptosis is a regulated, iron-dependent form of cell death driven by lipid peroxidation and distinct from apoptosis, necroptosis, pyroptosis. Recent studies implicate ferroptosis as central contributor to the pathogenesis renal fibrosis, hallmark chronic kidney disease associated with high morbidity progression end-stage failure. This review synthesizes current evidence linking ferroptotic signaling fibrotic remodeling in kidney, focusing on iron metabolism dysregulation, glutathione peroxidase 4 (GPX4) inactivation, peroxide accumulation, ferroptosis-regulatory pathways such FSP1-CoQ10-NAD(P)H GCH1-BH4. We detail how tubular epithelial cells modulates pro-fibrotic cytokine release, macrophage recruitment, TGF-β1-driven extracellular matrix deposition. Moreover, we explore therapeutic vulnerability highlighting promising agents including chelators, GPX4 activators, anti-lipid peroxidants, exosome-based gene delivery systems. By consolidating emerging preclinical data, this provides comprehensive mechanistic framework identifies translational opportunities for targeting disease.

Language: Английский

Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy DOI Creative Commons
Hua Miao, Yamei Zhang,

Xiao-Yong Yu

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 13, 2022

Membranous nephropathy (MN) is a renal-limited non-inflammatory autoimmune disease in the glomerulus, which second or third main cause of end-stage kidney diseases patients with primary glomerulonephritis. Substantial achievements have increased our understanding aetiology and pathogenesis murine human MN. The identification nephritogenic autoantibodies against neutral endopeptidase, phospholipase A 2 receptor (PLA R) thrombospondin type-1 domain-containing 7A (THSD7A) antigens provide more specific concept-driven intervention strategies for treatments by B cell-targeting monoclonal antibodies to inhibit antibody production antibody-antigen immune complex deposition. Furthermore, additional specificities been discovered, but their pathogenic effects are uncertain. Although anti-PLA R anti-THSD7A as diagnostic marker widely used MN patients, many questions including response development, antigenic epitopes, podocyte damage signalling pathways remain unresolved. This review describes current available evidence regarding both established novel molecular mechanisms based on systems biology approaches (gut microbiota, long non-coding RNAs, metabolite biomarkers DNA methylation) MN, an emphasis clinical findings. further summarizes applications traditional Chinese medicines such Tripterygium wilfordii Astragalus membranaceus treatment. Lastly, this considers how antibodies/antigens unresolved future challenges reveal

Language: Английский

Citations

27
Recent Advances in Clinical Diagnosis and Pharmacotherapy Options of Membranous Nephropathy DOI Creative Commons
Yanni Wang,

Hao-Yu Feng,

Xin Nie

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: May 26, 2022

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome among adults, which leading glomerular disease that recurs after kidney transplantation. Treatment for MN remained controversial and challenging, partly owing to absence sensitive specific biomarkers effective therapy prediction diagnosis activity. starts with formation deposition circulating immune complexes on outer area in basement membrane, complement activation. The identification autoantibodies against phospholipase A2 receptor (PLA2R) thrombospondin type-1 domain-containing protein 7A (THSD7A) antigens illuminated a distinct pathophysiological rationale treatments. Nowadays, detection serum anti-PLA2R antibodies deposited PLA2R antigen can be routinely applied MN. Anti-PLA2R exhibited much high specificity sensitivity. Measurement complex allows PLA2R-associated patients renal biopsies. In review, we critically summarized newer including THSD7A tests novel promising therapies by using traditional Chinese medicines such as Astragalus membranaceus, Tripterygium wilfordii, Astragaloside IV treatment patients. We also described unresolved questions future challenges reveal treatments These unprecedented breakthroughs were quickly translated clinical management. Considerable advances methods played critical role monitoring treatment.

Language: Английский

Citations

23
Ferroptosis: new insight into the mechanisms of diabetic nephropathy and retinopathy DOI Creative Commons
Luxin Li,

Yucen Dai,

Dan Ke

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 3, 2023

Diabetic nephropathy (DN) and diabetic retinopathy (DR) are the most serious common diabetes-associated complications. DN DR all highly prevalent dangerous global diseases, but underlying mechanism remains to be elucidated. Ferroptosis, a relatively recently described type of cell death, has been confirmed involved in occurrence development various The disturbance cellular iron metabolism directly triggers ferroptosis, abnormal is closely related diabetes. However, molecular role ferroptosis still unclear, needs further study. In this review article, we summarize evaluate its progress DR, it provides new ideas for diagnosis treatment DR.

Language: Английский

Citations

16
Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-β/Smad signaling pathway DOI Creative Commons
Chunjun Li,

Xiangxiang Meng,

Lina Wang

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 9, 2023

Cardiac fibrosis is a serious public health problem worldwide that closely linked to progression of many cardiovascular diseases (CVDs) and adversely affects both the disease process clinical prognosis. Numerous studies have shown TGF-β/Smad signaling pathway plays key role in cardiac fibrosis. Therefore, targeted inhibition may be therapeutic measure for Currently, as investigation on non-coding RNAs (ncRNAs) move forward, variety ncRNAs targeting TGF-β its downstream Smad proteins attracted high attention. Besides, Traditional Chinese Medicine (TCM) has been widely used treating As more molecular mechanisms natural products, herbal formulas, proprietary medicines are revealed, TCM proven act by modulating multiple targets pathways, especially TGF-β/Smad. this work summarizes roles classical non-classical pathways fibrosis, discusses recent research advances against It hoped, way, give new insights into prevention treatment

Language: Английский

Citations

15
Fucoidan from Saccharina japonica Alleviates Hyperuricemia-Induced Renal Fibrosis through Inhibiting the JAK2/STAT3 Signaling Pathway DOI
Lirui Sun, Qing Liu, Yabin Zhang

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(30), P. 11454 - 11465

Published: July 23, 2023

Fucoidan is a native sulfated polysaccharide mainly isolated from brown seaweed, with diverse pharmacological activities, such as anti-inflammatory and antifibrosis. Hyperuricemia (HUA) common metabolic disease worldwide causes hyperuricemic nephropathy, including chronic kidney end-stage renal fibrosis. The present study investigated the protective function of fucoidan in fibrosis its mechanism. fibrotic model was established administration potassium oxonate for 10 weeks. protein levels related factors were assessed HUA mice by an enzyme-linked immunosorbent assay (ELISA) western blotting. results showed that significantly reduced serum uric acid, blood urea nitrogen (BUN), α-smooth muscle actin (α-SMA), collagen I, improved pathological changes. Furthermore, had been remarkably elevated through inhibition epithelial-to-mesenchymal transition (EMT) progression after intervention, suppressing Janus kinase 2 (JAK2) signal transducer activator transcription 3 (STAT3) signaling pathway activation. Together, this provides experimental evidence may protect against hyperuricemia-induced via downregulation JAK2/STAT3 pathway.

Language: Английский

Citations

14
Osthole ameliorates early diabetic kidney damage by suppressing oxidative stress, inflammation and inhibiting TGF-β1/Smads signaling pathway DOI
Qiangsheng Li, Yifei Wang, Yan Jia

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 133, P. 112131 - 112131

Published: April 25, 2024

Language: Английский

Citations

5
Identification of ligand and receptor interactions in CKD and MASH through the integration of single cell and spatial transcriptomics DOI Creative Commons
Jaime Moreno, Lise Lotte Gluud, Elisabeth D. Galsgaard

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(5), P. e0302853 - e0302853

Published: May 20, 2024

Background Chronic Kidney Disease (CKD) and Metabolic dysfunction-associated steatohepatitis (MASH) are metabolic fibroinflammatory diseases. Combining single-cell (scRNAseq) spatial transcriptomics (ST) could give unprecedented molecular disease understanding at resolution. A more comprehensive analysis of the cell-specific ligand-receptor (L-R) interactions provide pivotal information about signaling pathways in CKD MASH. To achieve this, we created an integrative framework MASH from two available human cohorts. Results The analytical identified L-R pairs involved cellular crosstalk Interactions between cell types using scRNAseq data were validated by checking co-presence ST co-expression communicating targets. Multiple protein known key players MASH, while others novel potential targets previously observed only animal models. Conclusion Our study highlights importance integrating different modalities transcriptomic for a better mechanisms. combination resolution data, combined with tissue slide investigations visualization cell-cell obtained through ST, paves way identification future therapeutic developing effective therapies.

Language: Английский

Citations

4
Recent advances of gut microbiota in chronic kidney disease patients DOI Creative Commons
Ying‐Yong Zhao

Exploration of Medicine, Journal Year: 2022, Volume and Issue: unknown, P. 260 - 274

Published: June 23, 2022

Chronic kidney disease (CKD) is a worldwide public health issue and has ultimately progressed to an end-stage renal that requires life-long dialysis or transplantation. However, the underlying molecular mechanism of these pathological development progression remains be fully understood. The human gut microbiota made up approximately 100 trillion microbial cells including anaerobic aerobic species. In recent years, more evidence indicated clear association between dysbiosis CKD immunoglobulin A (IgA) nephropathy, diabetic disease, membranous chronic failure disease. current review describes metabolites in patients with thus helping understand Treatment prebiotics, probiotics natural products can attenuate through improving microbiota, indicating novel intervention strategy CKD. This also discusses therapeutic options, such as products, for targeting provide specific concept-driven therapy treatment.

Language: Английский

Citations

18
Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway DOI Creative Commons
Yanni Wang,

Hong-Jiao Liu,

Lili Ren

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 17, 2022

Chronic kidney disease (CKD) is a major worldwide public health problem. The increase in the number of patients with CKD and end-stage requesting renal dialysis or transplantation will progress to epidemic proportions next several decades. Although blocking renin-angiotensin system (RAS) has been used as first-line standard therapy hypertension CKD, still towards disease, which might be closely associated compensatory renin expression subsequent RAS blockade through homeostatic mechanism. Wnt/β-catenin signalling pathway master upstream regulator that controls multiple intrarenal genes. As regulates genes, we inferred this also implicated blood pressure control. Therefore, discovering new medications synchronously target genes necessary essential for effective treatment CKD. We hypothesized Shenkang injection (SKI), widely treat patients, ameliorate by inhibiting activation via pathway. To test hypothesis, adenine-induced rats angiotensin II (AngII)-induced HK-2 NRK-49F cells. Treatment SKI inhibited function decline, fibrosis. Mechanistically, abrogated increased protein elements, including angiotensin-converting enzyme type 1 receptor, well Wnt1, β-catenin downstream Snail1, Twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1 fibroblast-specific 1, rats, was verified AngII-induced Similarly, our results further indicated rhein isolated from attenuated decline epithelial-to-mesenchymal transition repressed hyperactive both This study first revealed targeting elements

Language: Английский

Citations

18
Astragalus Mongholicus Polysaccharides Alleviate Kidney Injury in Rats with Type 2 Diabetes Through Modulation of Oxidation, Inflammation, and Gut Microbiota DOI Open Access

Guoquan Xu,

Hai‐Sheng Yuan, Jingran Liu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1470 - 1470

Published: Feb. 10, 2025

We aimed to uncover the underlying mechanisms contributing therapeutic efficacy of Astragalus mongholicus Polysaccharides (mAPS) in alleviating diabetic nephropathy (DN). The rat model DN was subjected a high-sugar and high-fat diet (HSHFD) coupled with streptozotocin (STZ) injection. Our findings revealed that mAPS administration decreased fasting blood glucose (FBG), BUN, SCR, UA, MDA levels, while elevating serum GSH, GSH-PX, SOD activities rats (p < 0.05). Furthermore, there notable rise mRNA protein expression renal Nrf-2, GCLC, NQO1, HO-1 post treatment Additionally, supplementation led reduced TLR4, NLRP3, p-NF-κB, TGF-β, Smad4. Concurrently, exerted modulatory effect on gut microbiota, as evidenced by increased abundance Muribaculaceae, Ruminococcus_1, Phascolarctobacterium, Lachnoclostridium-related genera. Spearman correlation analysis illustrated negative association between microbiota (Muribaculaceae, Lachnospiraceae_NK4A136, Clostridiales) levels parameters (BUN, CR, TC, TG). In summary, our data robustly attests potential modulating oxidative stress, inflammation, ultimately resulting improved function rats.

Language: Английский

Citations

0