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

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
Dapagliflozin inhibits ferroptosis and ameliorates renal fibrosis in diabetic C57BL/6J mice DOI Creative Commons
Zhen Zhang, Luxin Li,

Yucen Dai

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 28, 2025

Diabetic nephropathy (DN) is a common complication of diabetes and major cause end-stage renal disease, with complex pathogenesis involving inflammation, oxidative stress, fibrosis, ferroptosis. Ferroptosis linked to DN progression, yet treatment options are limited, particularly for targeting Dapagliflozin (DAPA), an SGLT2 inhibitor, shows protective effects in diabetes, but its role fibrosis ferroptosis unclear. This study investigated DAPA's effect on by inhibiting ferroptosis, using streptozotocin-induced diabetic mouse model. Results indicated that DAPA improved function, reduced suppressed markers mice. In vitro, inhibited HK-2 cells under high glucose conditions. Molecular docking network pharmacology suggested anti-fibrotic anti-ferroptotic may involve the Nrf2 TGF-β signaling pathways. also serum creatinine blood urea nitrogen mice, glomerulosclerosis interstitial decreased iron deposition, enhanced antioxidant activity. Overall, multi-target mechanisms significantly improve suggesting potential as targeted therapy against Future studies should further explore applications.

Language: Английский

Citations

0
Jingtian granule alleviates adenine-induced renal fibrosis in mice through SIRT3-Mediated deacetylation of P53 DOI Creative Commons
Zhili Xiong, Xinyu Hu, Rui Wang

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 12, 2025

Background Renal fibrosis is a hallmark and the final outcome of chronic kidney disease (CKD). Jingtian Granule (JT), traditional formula used in clinical treatment CKD for many years. However, mechanism action JT against renal interstitial remain unknown. Objective This study aimed to explore potential effects mechanisms on adenine - diet induced mice. Methods was mice by treated with JT. function assessed measuring blood urea nitrogen serum creatinine levels. Masson’s staining type I collagen expression were evaluate deposition. RNA sequencing analyze levels mRNA mouse samples after treatment. The glutathione (GSH) malondialdehyde (MDA) measured assess lipid peroxidation kidneys. Iron metabolism detected Prussian blue measurement iron content. protein SIRT3, P53, peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) Western blot. Subsequently, under premise SIRT3 knockout, function, level, level detected, mitochondrial damage observed transmission electron microscope (TEM). In addition, human proximal tubule epithelial cells (HK 2) Erastin induce ferroptosis, followed exposure reactive oxygen species (ROS) detected. Results significantly reduced deposition identified 20 mRNAs that differentially expressed response Bioinformatics analysis revealed key regulated activated fibrotic kidneys inhibit acetylation P53. Under did not show significant therapeutic inhibiting ferroptosis fibrosis. vitro experiments also showed promoted downregulation ROS. Conclusion related ability modulate SIRT3/P53 signaling pathway may be viable approach

Language: Английский

Citations

0
Fermented Strawberry (Fragaria x Ananassa Duch.) Mitigates Renal Fibrosis in a Unilateral Ureteral Obstruction Model by Reducing Inflammation, Oxidative Stress, and Regulating Smad Signaling DOI
Chia‐Chu Chang,

Erl‐Shyh Kao,

Yi-Chen Lee

et al.

Journal of Medicinal Food, Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Renal fibrosis is a common outcome in many progressive renal diseases. Unilateral ureteral obstruction (UUO) known to induce oxidative stress and inflammation the kidneys, leading development of fibrosis. Fermented strawberry (Fragaria x ananassa Duch.) possesses antioxidant properties; however, its effect on remains unclear. This study aimed evaluate impact fermented dry powder (FSP) by assessing proinflammatory cytokines, markers, underlying mechanisms. Male Sprague-Dawley rats were subjected UUO surgery tubulointerstitial obstructive nephropathy. Ten days postsurgery, randomly divided into four groups (n = 6), including sham-operated control group. FSP was administered orally at doses 0.05 or 0.5 g kg-1 body weight daily for 21 days. treatment significantly improved function, reduced tubular dilation, decreased interstitial volume rats. levels tumor necrosis factor-α interleukin-6, while enhancing activities enzymes such as superoxide dismutase catalase. Treatment with resulted reduction collagen deposition kidneys 49% 69%, respectively, compared increased E-cadherin expression α-smooth muscle actin level Furthermore, transforming growth factor-β Smad2/3 upregulating Smad7 expression. These findings suggest that mitigates fibrosis, likely through modulation Smad signaling attenuation inflammation.

Language: Английский

Citations

0
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

Citations

0