Cellular Senescence in Metabolic-Associated Kidney Disease: An Update

Gao, Pan; Zou, Xingjian; Sun, Xin; Zhang, Chun

doi:10.3390/cells11213443

Cited by 13 publications

(8 citation statements)

References 54 publications

(84 reference statements)

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“…This condition is characterized by acute arthritis, tophi, interstitial nephritis, joint deformity, and dysfunction 29 , 30 , often accompanied by uric acid urolithiasis 31 . As the incidence of gout continues to rise, it can induce other symptoms, such as hyperglycemia, hyperlipidemia, kidney damage, and physical disability 32 , 33 . Existing studies have confirmed that MSU is related to the pathogenesis of gouty arthropathy as one of the incentives for gout 34 .…”

Section: Discussionmentioning

confidence: 99%

IL1A regulates the inflammation in gout through the Toll-like receptors pathway

Ling,

Gan,

et al. 2024

Int. J. Med. Sci.

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Objective: Gout is a dangerous metabolic condition related to monosodium urate (MSU). Our aim is to study the molecular mechanisms underlying gout and to identify potential clinical biomarkers by bioinformatics analysis and experimental validation. Methods: In this study, we retrieved the overlapping genes between GSE199950-Differential Expressed Genes (DEGs) dataset and key module in Weighted Gene Co-Expression Network Analysis (WGCNA) on GSE199950. These genes were then analyzed by protein-protein interaction (PPI) network, expression and Gene Set Enrichment Analysis to identify the hub gene related to gout. Then, the gene was investigated by peripheral blood mononuclear cells (PBMCs), immunoassay and cell experiments like western blotting to uncover its underlying mechanism in gout cells. Results: From the turquoise module and 83 DEGs, we identified 62 overlapping genes, only 11 genes had mutual interactions in PPI network and these genes were highly expressed in MSU-treated samples. Then, it was found that the IL1A (interleukin 1 alpha) was the only one gene related to Toll-like receptor signaling pathway that was associated with the occurrence of gout. Thus, IL1A was determined as the hub gene in this study. In immunoassay, IL1A was significantly positively correlated with B cells and negatively correlated with macrophages. Moreover, IL1A is highly expressed in gout patients,it has a good clinical diagnostic value. Finally, the results of in vitro experiments showed that after knocking down IL1A, the expressions of pro-inflammatory cytokines and Toll-like receptor signaling pathway-related proteins (TLR2, TLR4, MyD88) were all reduced. Conclusion: It is confirmed that IL1A is a promoting gene in gout with a good diagnostic value, and specifically it affects the inflammation in gout through Toll-like receptor pathway. Our research offers fresh perspectives on the pathophysiology of gout and valuable directions for future diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

IL1A regulates the inflammation in gout through the Toll-like receptors pathway

Ling,

Gan,

et al. 2024

Int. J. Med. Sci.

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“…Mitotic cell decline lessens to conserve energy in the channel to meet the energetic demands of iono-osmoregulation [41]. In recent studies, cyclin E expression was downregulated via the upregulation of p53/p21 genes and the activation of the p53 signaling pathway [42,43], and the activation of p53/p21 could be stimulated by cell stress [44]. miR-16 has been identified as a key effector of the p53 pathway in response to genotoxic stress and is reported to target several cell cycle regulators, including cyclin E, Chk1, cyclin D1, and Cdk6 in mammals [45].…”

Section: Discussionmentioning

confidence: 99%

The Identification of a Cell Cycle Regulation Gene Cyclin E from Hong Kong Oysters (Crassostrea hongkongensis) and Its Protein Expression in Response to Salinity Stress

Qiu,

Wang,

Yan

et al. 2024

Fishes

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Hong Kong oysters (Crassostrea hongkongensis) are an important marine bivalve with nutritional and commercial value. The expanded off-bottom farming scale in recent years makes the oysters more susceptible to exposure to abiotic stresses, such as salinity stress, an important environmental factor that has been proven to have significant effects on oyster growth and development. However, the molecular mechanism is still unclear. Cyclin E is an important protein in the process of cell cycle regulation that is indispensable for propelling G1/S phase transition in a dose-dependent manner. In order to investigate whether the salinity stress affects cyclin E expression in oysters, the cDNA sequence of C. hongkongensis cyclin E (Ch-CCNE) was isolated from a gill cDNA library, and the 2.8 kbp length cDNA fragment contained a complete open reading frame (ORF) encoding 440 amino acid residues. Ch-CCNE mRNA was highly expressed in the gonad and low in the adductor mussel, mantle, gill, labial palp, and digestive gland. The recombinant CCNE protein was expressed and purified in a pET32a(+)-CCNE/Escherichia coli BL21(DE3) system via IPTG induction and was used for generating mice anti-Ch-CCNE antiserums. Western blot analysis showed that the CCNE protein in the gill was maintained at low expression levels under either hypo- (5 ppt) or hyper- (35 ppt) salinity, and could be produced at high levels under appropriate salinity during a 10-day exposure period. The immuno-localization indicated that the Ch-CCNE protein was distributed in the nucleus. These results suggested that either hypo- or hyper-salinity stress could inhibit the CCNE expression of Hong Kong oysters and their negative impact on cell division and proliferation.

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“…Early DKD renal damage is caused by the accumulation of senescent cells and an increase in the degree of fibrosis. 24 AIP is calculated based on the ratio of TGs to HDL-C and is easily measurable in clinical practice. Apolipoprotein B is a component of TGs that contributes to the development of atherosclerosis, whereas apolipoprotein A1 is a component of HDL-C that has a protective effect against atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Atherogenic Index of Plasma as an Early Marker of Chronic Kidney Disease and Liver Injury in Type 2 Diabetes

Li,

Miao,

Zhong

et al. 2024

Clin Med Insights Endocrinol Diabetes

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Background: Diabetic kidney disease (DKD) is the main cause of end-stage renal disease and has a high mortality rate. Currently, no effective treatments are available to reduce the progression of kidney damage associated with diabetes. Objectives: To explore the influence and predictive value of the atherogenic index of plasma (AIP) on early chronic kidney disease and liver injury in patients with type 2 diabetes mellitus (T2DM). Methods: Medical records of 1057 hospitalized adult patients with T2DM between January 2021 and December 2022 were collected. The predictive value of AIP, renal function, and liver injury in patients with T2DM were analyzed using Pearson’s correlation, multiple logistic regression, and receiver operating characteristic (ROC) curve analyses. Results: AIP was a sensitive indicator of early liver and kidney injury in patients with T2DM. Patients in the DKD group showed increased AIP that positively correlated with serum creatinine, uric acid, and β2-microglobulin levels. Increased AIP negatively correlated with estimated glomerular filtration rate (eGFR). AIP significantly correlated with alanine aminotransferase and aspartate aminotransferase levels and glutamyl transpeptidase-to-platelet ratio (GPR). An eGFR of 60-100 mL/min/1.73 m2 significantly increased the risk of DKD as the AIP increased. At lower GPR levels, the risk of DKD significantly increased with increasing AIP. However, no significant difference was found between the 2 groups when the GPR was >0.1407. The ROC curve analysis showed that AIP could predict early liver injury. Conclusions: AIP is directly involved in early liver and kidney injury in T2DM and may be a sensitive indicator for early detection.

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Cellular Senescence in Metabolic-Associated Kidney Disease: An Update

Cited by 13 publications

References 54 publications

IL1A regulates the inflammation in gout through the Toll-like receptors pathway

IL1A regulates the inflammation in gout through the Toll-like receptors pathway

The Identification of a Cell Cycle Regulation Gene Cyclin E from Hong Kong Oysters (Crassostrea hongkongensis) and Its Protein Expression in Response to Salinity Stress

Atherogenic Index of Plasma as an Early Marker of Chronic Kidney Disease and Liver Injury in Type 2 Diabetes

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