KLF9, Epigenetic Silenced by DNMT1, Promotes ERK‐Mediated Ferroptosis of Osteoarthritic Chondrocytes Through Transcriptionally Regulating CYP1B1 DOI Creative Commons

Min Lv,

Yuanzhen Cai,

Weikun Hou

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(5)

Published: Feb. 27, 2025

ABSTRACT Ferroptosis plays a crucial role in the pathogenesis of osteoarthritis (OA), and inhibition chondrocyte ferroptosis effectively alleviates OA progression. Krüppel‐like factor 9 (KLF9) is demonstrated to be upregulated OA, but its molecular mechanism remains unclear. The study aimed investigate KLF9 Primary chondrocytes were treated with IL‐1β establish an cell model, showed that was highly expressed IL‐1β‐incubated chondrocytes. Knockdown alleviated IL‐1β‐induced degeneration. In addition, decreased methylation proportion gene promoter. DNA methyltransferase 1 (DNMT1) directly bound promoter, overexpression DNMT1 inhibited expression by promoting promoter Subsequently, shRNA pcDNA‐CYP1B1 individually or altogether transfected into Cytochrome P450 1B1 (CYP1B1) chondrocytes, abrogated inhibitory effect on ferroptosis. Moreover, Ferrostatin‐1 (Fer‐1, inhibitor ferroptosis) reversed promotion Finally, vivo experiments significantly suppressed cartilage tissue damage, ferroptosis, IHC scores CYP1B1 rats. conclusion, our results suggested KLF9, epigenetic silenced DNMT1, promoted extracellular signal‐regulated kinase (ERK)‐mediated through transcriptionally regulating CYP1B1. Thus, expected new target for treatment OA.

Language: Английский

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases DOI Creative Commons
Yumin Wang, Jing Hu, Shuang Wu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

Citations

72
Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy DOI Creative Commons
Xi Lu,

Qingxing Xie,

Xiaohui Pan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 2, 2024

Language: Английский

Citations

39
Ferroptosis: Mechanisms and role in diabetes mellitus and its complications DOI
Pan Liu, Zhengdong Zhang, Yichen Cai

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 94, P. 102201 - 102201

Published: Jan. 19, 2024

Language: Английский

Citations

37
Amino acid metabolism disorder and oxidative stress took part in EGCG alleviating Mn-caused ferroptosis via miR-9-5p/got1 axis DOI
Qin Zhou,

Zhiyu Hao,

Ming-Yue Qiu

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 489, P. 137656 - 137656

Published: Feb. 21, 2025

Language: Английский

Citations

3
Empagliflozin Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats by Modulating Sesn2/AMPK/Nrf2 Signaling and Targeting Ferroptosis and Autophagy DOI Open Access
Hemat El‐Sayed El‐Horany, Marwa Mohamed Atef, Muhammad Tarek Abdel Ghafar

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9481 - 9481

Published: May 30, 2023

Pulmonary fibrosis (PF) is a life-threatening disorder that severely disrupts normal lung architecture and function, resulting in severe respiratory failure death. It has no definite treatment. Empagliflozin (EMPA), sodium-glucose cotransporter 2 (SGLT2) inhibitor, protective potential PF. However, the mechanisms underlying these effects require further elucidation. Therefore, this study aimed to evaluate ameliorative effect of EMPA against bleomycin (BLM)-induced PF mechanisms. Twenty-four male Wister rats were randomly divided into four groups: control, BLM treated, EMPA+BLM treated. significantly improved histopathological injuries illustrated by both hematoxylin eosin Masson's trichrome-stained tissue sections, as confirmed electron microscopic examination. reduced index, hydroxyproline content, transforming growth factor β1 levels rat model. had an anti-inflammatory effect, evidenced decrease inflammatory cytokines' tumor necrosis alpha high mobility group box 1, cell infiltration bronchoalveolar lavage fluid, CD68 immunoreaction. Furthermore, mitigated oxidative stress, DNA fragmentation, ferroptosis, endoplasmic reticulum up-regulation nuclear erythroid 2-related expression, heme oxygenase-1 activity, glutathione peroxidase 4 levels, C/EBP homologous protein levels. This could be explained on basis autophagy induction via up-regulating sestrin2 expression LC3 II immunoreaction observed study. Our findings indicated protected BLM-induced PF-associated cellular stress enhancing modulating sestrin2/adenosine monophosphate-activated kinase/nuclear 2/heme oxygenase 1 signaling.

Language: Английский

Citations

33
Emerging significance and therapeutic targets of ferroptosis: a potential avenue for human kidney diseases DOI Creative Commons
Jinghan Li,

Sujuan Zheng,

Yumei Fan

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(9)

Published: Sept. 22, 2023

Abstract Kidney diseases remain one of the leading causes human death and have placed a heavy burden on medical system. Regulated cell contributes to pathology plethora renal diseases. Recently, with in-depth studies into kidney death, new iron-dependent modality, known as ferroptosis, has been identified attracted considerable attention among researchers in pathogenesis therapeutics treat them. The majority suggest that ferroptosis plays an important role pathologies multiple diseases, such acute injury (AKI), chronic disease, carcinoma. In this review, we summarize recently regulatory molecular mechanisms discuss pathways action various describe protective effect inhibitors against especially AKI. By summarizing prominent roles different progress made studying provide directions strategies for future research summary, ferroptotic factors are potential targets therapeutic intervention alleviate targeting them may lead treatments patients

Language: Английский

Citations

27
Role of ferroptosis in chronic kidney disease DOI Creative Commons
Shiyang Li, Qiuxia Han, Chang Liu

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 12, 2024

Abstract Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with gradual loss renal function, incidence various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt progression injury in emphasizing urgent need delve into precise molecular mechanisms governing occurrence development CKD while identifying novel therapeutic targets. Renal fibrosis, typical pathological feature plays pivotal role disrupting normal structures function. Ferroptosis recently discovered iron-dependent form cell death characterized by lipid peroxide accumulation. emerged potential key player diseases initiation organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute intricate interplay between its progression. This review comprehensively outlines relationship terms iron metabolism peroxidation, discusses current landscape pharmacological research on ferroptosis, shedding light promising avenues for intervention. It further illustrates recent breakthroughs ferroptosis-related regulatory implicated thereby providing new insights treatment.

Language: Английский

Citations

14
Empagliflozin ameliorates vascular calcification in diabetic mice through inhibiting Bhlhe40-dependent NLRP3 inflammasome activation DOI

Xiao-Xue Li,

Dong Chen, Xuejiao Sun

et al.

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(4), P. 751 - 764

Published: Jan. 3, 2024

Language: Английский

Citations

13
Chicoric acid advanced PAQR3 ubiquitination to ameliorate ferroptosis in diabetes nephropathy through the relieving of the interaction between PAQR3 and P110α pathway DOI Creative Commons
Wei Zhang, Yong Liu,

Jiajun Zhou

et al.

Clinical and Experimental Hypertension, Journal Year: 2024, Volume and Issue: 46(1)

Published: March 25, 2024

Purpose This study aimed to examine the impact of CA on DN and elucidate its underlying molecular mechanisms inflammation.

Language: Английский

Citations

12
Renal tubular epithelial cells response to injury in acute kidney injury DOI Creative Commons
Zuo‐Lin Li, Xinyan Li, Yan Zhou

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 107, P. 105294 - 105294

Published: Aug. 23, 2024

Acute kidney injury (AKI) is a clinical syndrome characterized by rapid and significant decrease in renal function that can arise from various etiologies, associated with high morbidity mortality. The tubular epithelial cells (TECs) represent the central cell type affected AKI, their notable regenerative capacity critical for recovery of afflicted patients. adaptive repair process initiated surviving TECs following mild AKI facilitates full recovery. Conversely, when severe or persistent, it allows to undergo pathological responses, abnormal phenotypic transformation, which will lead development fibrosis. Given implications fate after outcomes, deeper understanding these mechanisms necessary identify promising therapeutic targets biomarkers human kidney.

Language: Английский

Citations

10