Identification of potential anti aging drugs and targets in chronic kidney disease DOI Creative Commons
Qian Zhang, Bing Bai, Liang Ran

et al.

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

Published: May 3, 2025

Chronic kidney disease (CKD) is highly prevalent, incurable, and lacks effective treatments. Aging closely linked to various diseases. In this study, we combined CKD aging using bioinformatics approaches identify potential anti drugs therapeutic targets for CKD. We analyzed datasets GSE37171 GSE66494 from the GEO database, identifying 317 differentially expressed genes (DEGs). By intersecting these DEGs with related genes, identified 23 associated differential (ARDEGs). A protein-protein interaction (PPI) network was constructed STRING top 10 hub ARDEGs were Cytoscape software. Potential drugs, including Cinnamaldehyde, through ceRNA transcription factor regulatory networks, as well DGldb database. Among key in patient samples SOD2, FGF21, FOS, RELA, DDIT4, BMI1, DUSP6, LGALS3, CXCR2, CEBPB. Cinnamaldehyde other found target pathways, suggesting their delay progression modulating pathways. Finally, verified low-expression of DDIT4 two unilateral ureteral obstruction (UUO) animal model. Additionally, shown reduce expression fibrosis markers such fibronectin (FN) α-smooth muscle actin (α-SMA) HK2 cells under TGF-β1 stimulation. This study provides a foundational understanding molecular offers new directions developing therapies treat

Language: Английский

Renoprotective mechanisms of celastrol in high glucose-mediated HK-2 cell injury through inhibition of the PI3K/Akt/NF-κB signalling pathway DOI

Xiaojuan Wang,

Mohamad Hafizi Abu Bakar, Mohd Asyraf Kassim

et al.

Biochemistry and Biophysics Reports, Journal Year: 2025, Volume and Issue: 41, P. 101928 - 101928

Published: Jan. 28, 2025

Language: Английский

Citations

3
Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation DOI Creative Commons
Xiaoyao Zhang, Li Li,

Huishi Tan

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 14(1), P. 420 - 435

Published: Dec. 5, 2023

Klotho deficiency is a common feature of premature aging and chronic kidney disease (CKD). As such, restoring expression could be logic strategy for protecting against various nephropathies. In this study, we demonstrate that KP1, Klotho-derived peptide, inhibits cellular senescence by endogenous expression.

Language: Английский

Citations

23
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
Macrophage-derived exosomes promote telomere fragility and senescence in tubular epithelial cells by delivering miR-155 DOI Creative Commons

Qing Yin,

Tao-Tao Tang,

Xiaoyu Lu

et al.

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

Published: July 10, 2024

Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden substantial growing. CKD displays a number of features accelerated senescence. Tubular cell senescence common biological process that contributes to progression. Tubulointerstitial inflammation driver tubular characteristic CKD. However, the mechanism by which interstitial drives remains unclear. This paper aims explore role exosomal miRNAs derived from macrophages in development

Language: Английский

Citations

10
TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review) DOI Creative Commons
Jianchun Li, Yuanxia Zou, Jiraporn Kantapan

et al.

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 30(2)

Published: June 18, 2024

The TGF‑β/Smad signaling pathway plays a pivotal role in the onset of glomerular and tubulointerstitial fibrosis chronic kidney disease (CKD). present review delves into intricate post‑translational modulation this its implications CKD. Specifically, impact on various biological processes was investigated, encompassing not only renal tubular epithelial cell apoptosis, inflammation, myofibroblast activation cellular aging, but also autophagy. Various modifications (PTMs), including phosphorylation ubiquitination, play crucial modulating intensity persistence pathway. They dictate functionality, stability interactions components. sheds light recent findings regarding PTMs TGF‑β receptors Smads within CKD landscape. In summary, deeper insight intricacies offers avenues for innovative therapeutic interventions to mitigate progression. Ongoing research domain holds potential unveil powerful antifibrotic treatments, aiming preserve integrity function patients with

Language: Английский

Citations

8
Inflammation and aging-related disease: A transdisciplinary inflammaging framework DOI
Brian J. Andonian, Joseph A. Hippensteel, Katrina Abuabara

et al.

GeroScience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

8
Mitigation of Cardiovascular Disease and Toxicity through NRF2 Signalling DOI Open Access
James A. Roberts, Richard D. Rainbow, Parveen Sharma

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6723 - 6723

Published: April 4, 2023

Cardiovascular toxicity and diseases are phenomena that have a vastly detrimental impact on morbidity mortality. The pathophysiology driving the development of these conditions is multifactorial but commonly includes perturbance reactive oxygen species (ROS) signalling, iron homeostasis mitochondrial bioenergetics. transcription factor nuclear erythroid 2 (NFE2)-related (NRF2), master regulator cytoprotective responses, drives expression genes provide resistance to oxidative, electrophilic xenobiotic stresses. Recent research has suggested stimulation NRF2 signalling pathway can alleviate cardiotoxicity hallmarks cardiovascular disease progression. However, dysregulation dynamic responses be severely impacted by ageing processes off-target from clinical medicines including anthracycline chemotherapeutics, rendering cells system susceptible subsequent tissue dysfunction. This review addresses current understanding mechanisms under homeostatic pathophysiological within context wider implications for this diverse factor.

Language: Английский

Citations

14
Renal tubular epithelial cell quality control mechanisms as therapeutic targets in renal fibrosis DOI Creative Commons
Yini Bao, Qiyuan Shan, Keda Lu

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2024, Volume and Issue: 14(8), P. 100933 - 100933

Published: Jan. 4, 2024

Renal fibrosis is a devastating consequence of progressive chronic kidney disease, representing major public health challenge worldwide. The underlying mechanisms in the pathogenesis renal remain unclear, and effective treatments are still lacking. tubular epithelial cells (RTECs) maintain function, their dysfunction has emerged as critical contributor to fibrosis. Cellular quality control comprises several components, including telomere homeostasis, ubiquitin-proteasome system, autophagy, mitochondrial homeostasis (mitophagy metabolism), endoplasmic reticulum (unfolded protein response), lysosomes. Failures cellular RTECs, deoxyribonucleic acid (DNA), protein, organelle damage, exert profibrotic functions by leading senescence, defective stress, lysosomal dysfunction, apoptosis, fibroblast activation, immune cell recruitment. In this review, we summarize recent advances understanding role components intercellular crosstalk networks within context

Language: Английский

Citations

6
Enhanced TRPC3 transcription through AT1R/PKA/CREB signaling contributes to mitochondrial dysfunction in renal tubular epithelial cells in D‐galactose‐induced accelerated aging mice DOI Creative Commons
Bin Wang,

Wenpei Yu,

Weiguang Zhang

et al.

Aging Cell, Journal Year: 2024, Volume and Issue: 23(6)

Published: Feb. 28, 2024

Abstract Aging‐associated renal dysfunction promotes the pathogenesis of chronic kidney disease. Mitochondrial in tubular epithelial cells is a hallmark senescence and leads to accelerated progression disorders. Dysregulated calcium profiles mitochondria contribute aging‐associated disorders, but detailed mechanism this process not clear. In study, modulation sirtuin 1/angiotensin II type 1 receptor (Sirt1/AT1R) pathway partially attenuated glomerular sclerosis, atrophy, interstitial fibrosis D‐galactose (D‐gal)‐induced aging mice. Moreover, Sirt1/AT1R improved mitochondrial induced by D‐gal treatment. Transient potential channel, subtype C, member 3 (TRPC3) upregulation mediated dysregulated cellular homeostasis during aging. Furthermore, knockdown or knockout (KO) Trpc3 mice ameliorated D‐gal‐induced reactive oxygen species production, membrane deterioration, energy metabolism disorder. Mechanistically, activation AT1R/PKA promoted CREB phosphorylation nucleation CRE2 binding promoter (−1659 −1648 bp) enhance transcription. KO significantly disorder cell Taken together, these results indicate that TRPC3 mediates age‐related associated with overload dysfunction. promising therapeutic target for

Language: Английский

Citations

5
The complement system in the pathogenesis and progression of kidney diseases: What doesn't kill you makes you older DOI
Emma Diletta Stea,

Giuseppina D’Ettorre,

Adele Mitrotti

et al.

European Journal of Internal Medicine, Journal Year: 2024, Volume and Issue: 124, P. 22 - 31

Published: March 8, 2024

Language: Английский

Citations

5