IGF2BP3/NCBP1 complex inhibits renal tubular senescence through regulation of CDK6 mRNA stability

Translational research, Год журнала: 2024, Номер 273, С. 1 - 15

Опубликована: Июнь 28, 2024

Язык: Английский

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Lysosomal-Associated Protein Transmembrane 5, Tubular Senescence, and Progression of CKD

Journal of the American Society of Nephrology, Год журнала: 2024, Номер unknown

Опубликована: Июль 30, 2024

Key Points Lysosomal-associated protein transmembrane 5 (LAPTM5) is increased in tubular epithelial cells CKD. Conditional knockout of Laptm5 tubules attenuates kidney fibrosis mice with LAPTM5 contributes to senescence by inhibiting WWP2-mediated ubiquitination notch1 intracellular domain. Background Tubular a major determinant CKD, and identification potential therapeutic targets involved senescent has clinical importance. key molecule related T- B-cell receptor expression inflammation. However, the pattern contribution development CKD are unknown. Methods −/− tubule specific– were used examine role establishing different experimental mouse models. Results was significantly induced kidney, especially proximal distal convoluted tubules, from aristolochic acid nephropathy, bilateral ischemia/reperfusion injury–induced or unilateral ureter obstruction. Tubule-specific deletion inhibited alleviated tubulointerstitial aged mice. Moreover, deficiency ameliorated injury Mechanistically, domain mediating WWP2 lysosomal degradation then leading cellular cells. We also observed higher patients level correlated people Conclusions contributed regulating WWP2/notch1 signaling pathway exacerbated during progression

Язык: Английский

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Asiatic acid alleviates cisplatin-induced renal fibrosis in tumor-bearing mice by improving the TFEB-mediated autophagy-lysosome pathway

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 165, С. 115122 - 115122

Опубликована: Июль 4, 2023

Nephrotoxicity is a major side effect of cisplatin treatment solid tumors in the clinical setting. Long-term low-dose administration causes renal fibrosis and inflammation. However, few specific medicines with application value have been developed to reduce or treat nephrotoxic effects without affecting its tumor-killing effect. The present study analyzed potential reno-protective mechanism asiatic acid (AA) long-term cisplatin-treated nude mice suffering from tumors. AA significantly attenuated injury, inflammation, induced by injection tumor-bearing mice. notably suppressed tubular necroptosis improved autophagy-lysosome pathway disruption caused chronic tumor-transplanted HK-2 cells. promoted transcription factor EB (TFEB)-mediated lysosome biogenesis reduced accumulation damaged lysosomes, resulting enhanced autophagy flux. Mechanistically, increased TFEB expression rebalancing Smad7/Smad3, whereas siRNA inhibition Smad7 abolished on flux In addition, did not weaken, but actually anti-tumor cisplatin, as evidenced tumor apoptosis inhibited proliferation summary, alleviates cisplatin-induced improving TFEB-mediated pathway.

Язык: Английский

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C‐X‐C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through β‐catenin‐inhibited fatty acid oxidation

Journal of Cellular and Molecular Medicine, Год журнала: 2024, Номер 28(3)

Опубликована: Янв. 11, 2024

Abstract The prevalence of chronic kidney disease (CKD) is highly increasing. Renal fibrosis a common pathological feature in various CKD. Previous studies showed tubular cell senescence involved the pathogenesis renal fibrosis. However, inducers and underlying mechanisms have not been fully investigated. C‐X‐C motif chemokine receptor 4 (CXCR4), G‐protein‐coupled seven‐span transmembrane receptor, increases plays an important role injury. Whereas, whether CXCR4 could induce detailed studied yet. In this study, we adopted adriamycin nephropathy 5/6 nephrectomy models, cultured line. Overexpression or knockdown was obtained by injection related plasmids. We identified increased injury cells. expressed predominantly epithelial cells co‐localized with adipose differentiation‐related protein (ADRP) as well senescence‐related P16 INK4A . Furthermore, found overexpression greatly induced activation β‐catenin, while inhibited it. also that fatty acid oxidation triggered lipid deposition To inhibit β‐catenin ICG‐001, inhibitor significantly block CXCR4‐suppressed oxidation. Taken together, our results indicate key mediator promotes inducing inhibiting metabolism. Our findings provide new theory for

Язык: Английский

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Effects of Fisetin Treatment on Cellular Senescence of the Brain and Other Multiple Organs of Old Sheep

Опубликована: Июнь 27, 2023

Fisetin has been shown to be beneficial for brain injury and age-related disease via different mechanisms. The purpose of this study was determine the presence senescent cells effects fisetin on cellular senescence in other organs old sheep, a more translational model. Approximately 6-7 years female sheep (N=6) were treated with 100mg/kg or vehicle two consecutive days week 8 weeks. All harvested at time sacrifice. Histology, immunofluorescent staining, as well Q-PCR performed regions tissues organs. Our results indicated that treatment current regimen did not affect general morphology brain. both cerebral cortex cerebellum detected by SA-β-Gal staining. More observed gray matter when compared white cortex. These are mainly neurons either cerebellum. showed trend decrease significantly decreased matter. Furthermore, P16+ NEUN+ neurons, GFAP+ astrocytes, IBA+ microglia also astrocytes non- (Cornu Ammonis) CA area hippocampus. However, change CA1-4 At mRNA level, GLB1 heart ventricle muscle tissue spleen but tested. antioxidant gene SOD1 increased CAT bone marrow. variable SASP inflammasome genes In conclusion, we found widely present sheep. addition, non-CA represents promising therapeutic strategy disease.

Язык: Английский

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