Genetic and pharmacological tools to study the role of discoidin domain receptors in kidney disease DOI Creative Commons
Corina M. Borza, Gema Bolás, Ambra Pozzi

et al.

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

Published: Sept. 28, 2022

Following injury the kidney undergoes a repair process, which results in replacement of injured tissue with little evidence damage. However, repetitive injuries or inability to stop process result abnormal deposition extracellular matrix (ECM) components leading fibrosis and organ dysfunction. The synthesis/degradation ECM is finely regulated by several factors, including discoidin domain receptors (DDRs). These are receptor tyrosine kinases that activated collagens. Upon activation, DDRs control cell functions that, when exacerbated, contribute fibrosis. undetectable healthy kidney, but become rapidly upregulated fibrotic conditions, thus making them attractive anti-fibrotic targets. promoting apoptosis cells, stimulating production pro-inflammatory cytokines, regulating components. They achieve these effects activating canonical intracellular molecules directly interacting nuclear chromatin transcription pro-fibrotic genes. goal this review highlight non-canonical mechanisms whereby injury/fibrosis. This will summarize key findings obtained using cells mice lacking it discuss discovery development targeted DDR small molecule- antisense-based inhibitors. Understanding molecular might enable us not only develop more selective potent inhibitors, also determine inhibition needs be achieved prevent and/or halt

Language: Английский

Lachnospiraceae-bacterium alleviates ischemia-reperfusion injury in steatotic donor liver by inhibiting ferroptosis via the Foxo3-Alox15 signaling pathway DOI Creative Commons
Shenghe Deng, Huan Cao,

Tongxi Li

et al.

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 30, 2025

Ischemia-reperfusion injury (IRI) is a major obstacle in liver transplantation, especially with steatotic donor livers. Dysbiosis of the gut microbiota has been implicated modulating IRI, and Lachnospiraceae plays pivotal role regulating host inflammatory immune responses, but its specific transplantation IRI remains unclear. This study explores whether can mitigate underlying mechanisms. We found Lachnospiraceae-bacterium (Lachn.) abundance was significantly reduced rats cirrhosis. Lachn.-treated exhibited improved intestinal permeability, severity both normal livers, decreased levels neutrophil macrophage infiltration, cytokines. Multi-omics analysis revealed elevated pyruvate transplanted livers after Lachn. treatment, alongside Alox15 Foxo3 expression. Mechanistically, Lachn.-derived inhibited expression ferroptosis Furthermore, nuclear translocation further suppressed expression, alleviating Clinical samples confirmed cirrhotic recipients high transplantation. In conclusion, alleviates by inhibiting via Foxo3-Alox15 axis, providing potential therapeutic strategy to modulate alleviate following

Language: Английский

Citations

3
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

14
The forkhead box O3 (FOXO3): a key player in the regulation of ischemia and reperfusion injury DOI
Moussa Omorou, Yiwei Huang, Meng Gao

et al.

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(4)

Published: March 20, 2023

Language: Английский

Citations

18
Impaired TFEB-mediated autophagy-lysosome fusion promotes tubular cell cycle G2/M arrest and renal fibrosis by suppressing ATP6V0C expression and interacting with SNAREs DOI Creative Commons
Xiang Ren, Jing Wang,

Huizhi Wei

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(5), P. 1905 - 1926

Published: Jan. 1, 2024

Increasing evidence suggests that autophagy plays a major role during renal fibrosis.Transcription factor EB (TFEB) is critical regulator of autophagy-and lysosome-related gene transcription.However, the pathophysiological roles TFEB in fibrosis and fine-tuned mechanisms by which regulates remain largely unknown.Here, we found was downregulated unilateral ureteral obstruction (UUO)-induced human mouse fibrotic kidneys, kidney-specific overexpression using recombinant AAV serotype 9 (rAAV9)-TFEB UUO mice alleviated pathogenesis.Mechanically, TFEB's prevention extracellular matrix (ECM) deposition depended on autophagic flux integrity its subsequent blockade G2/M arrest tubular cells, rather than autophagosome synthesis.In addition, together RNA-seq with CUT&Tag analysis to determine targeted ATP6V0C, revealed directly bound ATP6V0C promoter only at specific site promote expression through CUT&Run-qPCR luciferase reporter assay.Interestingly, induced integrity, mainly dependent scaffold protein ATP6V0C-mediated autophagosome-lysosome fusion bridging STX17 VAMP8 (major SNARE complex) co-immunoprecipitation analysis, mediated lysosomal acidification degradation function.Moreover, further investigated underlying mechanism behind low TEFB UUO-induced fibrosis, clearly suppression kidney due DNMT3a-associated hypermethylation utilizing methylation PCR (MSP) bisulfite-sequencing (BSP), could be effectively recovered 5-Aza-2'-deoxycytidine (5A-za) alleviate pathogenesis.These findings reveal for first time impaired TFEB-mediated disorder, cell appear sequentially linked suggest DNMT3a/TFEB/ATP6V0C may serve as potential therapeutic targets prevent fibrosis.

Language: Английский

Citations

6
Dysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation DOI Creative Commons
Yaechan Song,

Heeju Na,

Seung Eon Lee

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 14, 2024

Obesity has emerged as a prominent risk factor for the development of malignant tumors. However, existing literature on role adipocytes in tumor microenvironment (TME) to elucidate correlation between obesity and cancer remains insufficient. Here, we aim investigate formation cancer-associated (CAAs) their contribution growth using mouse models harboring dysfunctional adipocytes. Specifically, employ adipocyte-specific BECN1 KO (BaKO) mice, which exhibit lipodystrophy due Our results reveal activation YAP/TAZ signaling both CAAs BECN1-deficient adipocytes, inducing adipocyte dedifferentiation TME. The additional deletion from BaKO mice significantly restores inflammatory phenotypes, leading regression. Furthermore, fed high-fat diet (HFD) decreased increased expression adipose tissues. Treatment with inhibitor, verteporfin, suppresses progression HFD-fed highlighting its efficacy against metabolic dysregulation. Overall, our findings provide insights into key mediators CAA significance developing TME, thereby suggesting viable approach targeting homeostasis suppress growth.

Language: Английский

Citations

6
BK Polyomavirus and acute kidney injury in transplant recipients: signaling pathways and molecular mechanisms DOI Creative Commons

Samar Bizhani,

Afsoon Afshari, Ramin Yaghobi

et al.

Virology Journal, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 4, 2025

Acute kidney injury (AKI) is a condition that can result in changes both urine production and creatinine levels the bloodstream, complicating treatment process worsening outcomes for many hospitalized patients. BK polyomavirus (BKPyV), member of Polyomaviridae family, prevalent population remains latent body. It reactivate individuals with compromised immune system, particularly post-kidney transplant, activate various transcription factors mediators. Although reactivation often asymptomatic, it present as AKI, which risk factor early loss transplanted organ. The response to BKPyV crucial controlling virus safeguarding organs from damage during infection. Understanding pathways may offer novel opportunities effectively treating BKPyV-associated complications. This review seeks elucidate potential mechanisms by lead AKI analyzing signaling pathways, well identification molecular utilize induce AKI.

Language: Английский

Citations

0
IL‐17A Induces Circadian Disruptions Through the Epigenetic Repression of BMAL1 in Mice With Alzheimer's Disease DOI Creative Commons
Ting Liu,

Mao Tian,

Jin‐Xuan Fan

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(7)

Published: April 1, 2025

ABSTRACT Circadian disruptions and neuroinflammation impact nearly all people with Alzheimer's disease (AD), but their relationships each other the of interaction on AD remain to be addressed. Here, we found that amyloid (A)‐β treatment downregulated brain muscle aryl hydrocarbon receptor nuclear translocator‐like (BMAL) 1 through hypermethylation its promoter region in HT22 cells inhibition DNA methylation ameliorated circadian rhythm disorders restored BMAL1 protein expression by reversing APPswe/PSEN1dE9 (APP/PS1) mice. Critically, increased levels interleukin (IL)‐17A contributed downregulation region, thus leading APP/PS1 Moreover, revealed mitogen‐activated kinase (MAPK) pathway was responsible for IL‐17A‐induced methyltransferase (DNMT) upregulation. Taken together, elucidate a new mechanism connecting IL‐17A altered Bmal1 , which results disturbances an mouse model.

Language: Английский

Citations

0
Remimazolam attenuates inflammation and kidney fibrosis following folic acid injury DOI
Jinfang Song, Wenqiang Yu,

Shuangquan Chen

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 966, P. 176342 - 176342

Published: Jan. 28, 2024

Language: Английский

Citations

3
IL-6 and diabetic kidney disease DOI Creative Commons
Lei Zhang,

Futian Xu,

Liyan Hou

et al.

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

Published: Dec. 19, 2024

Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes associated with high mortality and disability rates. Inflammation has emerged as key pathological mechanism in DKD, prompting interest novel therapeutic approaches targeting inflammatory pathways. Interleukin-6 (IL-6), well-established cytokine known for mediating various responses, attracted great attention the DKD field. Although multiple

Language: Английский

Citations

3
Embryonic exposure to prednisone induces bone developmental toxicity in zebrafish: characteristics and molecular mechanisms DOI
Jiaqi Wang,

Yangfan Shangguan,

Fei Long

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: unknown, P. 137996 - 137996

Published: March 1, 2025

Language: Английский

Citations

0